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Elevated HIF-1α induces cisplatin resistance in gastric cancer. A. The IC50 of cisplatin in SGC-7901 and AGS is 2.4 ± 0.66 μM and 20.8 ± 4.50 μM respectively. After being treated with CoCl 2 for 24h, the IC50 of cisplatin in SGC-7901 increases to 72.1 ± 5.20 μM, and AGS to 82.3 ± 4.70 μM. Error bars mean 95 % confidence intervals. Columns mean of three independent experiments, and bars SD. B. Flow cytometry analysis indicates that cisplatin drastically increases the percentage of early apoptotic cells in both cell lines, which could be attenuated by induction of CoCl 2 . Representative images and quantitative analysis of cell apoptosis are presented. Columns mean of three independent experiments, and bars SD. C. CoCl 2 increases the colony forming ability in cisplatin treated gastric cell lines compared with those treated with cisplatin alone. Representative images and quantitative analysis of colony formation rate are presented. Columns mean of three independent experiments, and bars SD. D. Transwell assays illustrate that cisplatin decreases the migration and invasion ability of both cell lines, and the inhibitory effect could be reversed by induction of CoCl 2 Representative migration and invasion images at ×100, and quantitative analysis of transwell assays are presented. Columns mean of three independent experiments, and bars SD. E. Western blot analysis shows that the expression of HIF-1α is significantly increased by CoCl 2 . The expression of cleaved caspase-3 and cleaved PARP are induced by cisplatin, E-cadherin is increased, and N-cadherin, Fibronectin, Vimentin, and Snail are decreased by cisplatin, which could be reversed by CoCl 2 in both cell lines. The E-cadherin is significantly down regulated, whereas N-cadherin, Fibronectin, Vimentin, and Snail are up regulated when treated with CoCl 2 alone. *P<0.05; **P<0.01; ***P < 0.001.
Source publication
Hypoxia and dysregulation of microRNAs (miRNAs) have been identified as crucial factors in carcinogenesis. However, the potential mechanisms of HIF-1α and miR-421 in gastric cancer have not been well elucidated. In this study, we found that miR-421 was up-regulated by HIF-1α. Overexpression of miR-421 promoted metastasis, inhibited apoptosis, and i...
Contexts in source publication
Context 1
... IC50 of cisplatin in SGC-7901 and AGS gastric cancer cell lines were 2.4 ± 0.66 μM and 20.8 ± 4.50 μM. After treated with CoCl 2 for 24h, the IC50 of cisplatin in both cell lines increased to 72.1 ± 5.20 μM and 82.3 ± 4.70μM, respectively ( Figure 2A). ...
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... cytometry analysis indicated that cisplatin drastically increased the percentage of early apoptotic cells in both cell lines. The apoptotic ability was attenuated by induction of CoCl 2 ( Figure 2B). Furthermore, CoCl 2 increased the colony forming ability in cisplatin treated gastric cell lines. ...
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... CoCl 2 increased the colony forming ability in cisplatin treated gastric cell lines. Compared with cell lines treated cisplatin alone, the colony formation ability increased drastically in cisplatin and CoCl 2 group ( Figure 2C). Besides, western blotting analysis indicated that cisplatin significantly elevated the expression of cleaved caspase-3 and cleaved PARP, which could be reversed by induction of CoCl 2 , indicating that CoCl 2 -induced HIF-1α suppressed the cisplatin-induced apoptosis ( Figure 2E). ...
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... with cell lines treated cisplatin alone, the colony formation ability increased drastically in cisplatin and CoCl 2 group ( Figure 2C). Besides, western blotting analysis indicated that cisplatin significantly elevated the expression of cleaved caspase-3 and cleaved PARP, which could be reversed by induction of CoCl 2 , indicating that CoCl 2 -induced HIF-1α suppressed the cisplatin-induced apoptosis ( Figure 2E). ...
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... further elucidate the function of HIF-1α in gastric cancer, we investigated the effect of CoCl 2 on cisplatin- treated SGC-7901 and AGS cell motility via transwell assay. The results suggested that cisplatin decreased the migration and invasion ability of both cell lines, and the inhibitory effect could be reversed by induction of CoCl 2 ( Figure 2D). EMT is an important process in invasion and metastasis of cancer and the loss expression of E-cadherin is a key factor in EMT. ...
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... a result, the expression of E-cadherin was increased, and that of N-cadherin, Fibronectin, Vimentin and Snail was decreased by cisplatin. However, the increased expression of E-cadherin and the decreased expression of N-cadherin, Fibronectin, Vimentin and Snail were attenuated by induction of CoCl 2 in both cell lines ( Figure 2E). Besides, we also found that the epithelial biomarker E-cadherin was significantly down regulated, whereas the mesenchymal biomarkers N-cadherin, Fibronectin, Vimentin and Snail were up regulated when treated with CoCl 2 alone ( Figure 2E). ...
Context 7
... the increased expression of E-cadherin and the decreased expression of N-cadherin, Fibronectin, Vimentin and Snail were attenuated by induction of CoCl 2 in both cell lines ( Figure 2E). Besides, we also found that the epithelial biomarker E-cadherin was significantly down regulated, whereas the mesenchymal biomarkers N-cadherin, Fibronectin, Vimentin and Snail were up regulated when treated with CoCl 2 alone ( Figure 2E). ...
Context 8
... of miR-421 reverses the function of HIF-1α. The results indicated that CoCl2 or miR-421 drastically decrease the percentage of apoptotic cells and increase the migration and invasion ability in cisplatin treated SGC-7901 and AGS cells, which could be reversed by transfection of miRNA-421 inhibitor (miR-421-Inh) together with CoCl2 (Supplementary Figure S2). These results indicated that HIF-1α is a key factor in regulation of miR-421. ...
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Citations
... miR-421 levels significantly increased in the hepatocytes and exosomes under intermittent hypoxia. Ge [52] reported that hypoxia induction can trigger miR-421 overexpression and promote gastric cancer metastasis and drug resistance. Additionally, in cardiomyocytes, the decrease in SIRT3 protein induced by hypoxia/reoxygenation is closely associated with the increase in miR-421 [53], consistent with our findings. ...
Purpose
To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD).
Methods
The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro.
Results
OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421−/− mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced.
Conclusions
OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD.
... These data confirmed the hypothesis that autophagy induced by hypoxia may serve as a survival strategy for OSCC cells. Previous studies found that HIF-1α was associated with the development and poor prognosis in many cancers, including gastric cancer, breast cancer, and lung cancer, and could change the biological function of a series of genes [41][42][43] . Interestingly, circCDR1as expression was increased by hypoxia exposure and played a role in tumor growth under a hypoxic environment in OSCC. ...
... The expression levels of HIF-1α increase in the cancer cells upon treatment with these agents independently. HIF-1α expression was found to be stabilized by cobalt chloride and dimethyloxalylglycine, and increased levels of HIF-1α triggered resistance to cisplatin in gastric cancer cells [112]. It was found that HIF-1α transcriptionally induces the expression of miR-421 and subsequently miR-421 targets E-cadherin and caspase-3 to promote metastasis and cisplatin resistance in gastric cancer [112]. ...
... HIF-1α expression was found to be stabilized by cobalt chloride and dimethyloxalylglycine, and increased levels of HIF-1α triggered resistance to cisplatin in gastric cancer cells [112]. It was found that HIF-1α transcriptionally induces the expression of miR-421 and subsequently miR-421 targets E-cadherin and caspase-3 to promote metastasis and cisplatin resistance in gastric cancer [112]. In addition to chemotherapy, miRNAs can also determine the response of cancer cells to radiation therapy. ...
The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1α is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1α. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1α with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1α and ncRNAs have been discussed in this article.
... Several other studies have also shown aberrant expression of a number of other circulating miRNAs, such as miR-129-1-3p, miR-129-2-3p and miR-421, in gastric juice, which may also be good candidates as non-invasive biomarkers in GC (Zhang et al., 2012;Yu et al., 2013). After all, there is evidence that some of these circulating miRNAs, like miR-421, are involved in oncogenic activity, and the authors found them in low amounts in GC patients (Ge et al., 2016;Yang et al., 2017;Jingyue et al., 2019). There are suggestions that these miRNAs may be involved in the process of crosstalk in the tumor microenvironment by being secreted into the gastric juice. ...
Gastric cancer (GC), being one of the most common malignant human tumors, occupies the second position in the structure of mortality in men and women. High rates of morbidity and mortality in this pathology determine its extremely high clinical and social significance. Diagnosis and timely treatment of precancerous pathology is the main way to reduce morbidity and mortality, and early detection of GC and its adequate treatment improve prognosis. The ability to accurately predict the development of GC and start treatment on time, as well as the ability to determine the stage of the disease if the diagnosis is confirmed - non-invasive biomarkers can become the key to solving these and many other problems of modern medicine. One of the promising biomarkers being studied are non-coding RNAs, namely, miсroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They are involved in a wide range of processes, including apoptosis, proliferation, differentiation, angiogenesis, which play a critical role in the development of GC oncogenesis. In addition, they are quite specific and stable due to their carriers (extracellular vesicles or Argonaute 2 protein) and can be detected in various human biological fluids, in particular gastric juice. Thus, miRNAs, lncRNAs, and circRNAs isolated from the gastric juice of GC patients are promising preventive, diagnostic and prognostic non-invasive biomarkers. This review article presents the characteristics of circulating or extracellular miRNAs, lncRNAs, and circRNAs in gastric juice, allowing their use in the GC preventive, diagnosis, prognosis and monitoring therapy.
... Zhao et al. found that HIF-1α/miR-17-5p axis may contribute to the tumor growth and metastasis of GC by negatively regulating programmed cell death 4 (PDCD4). 461 On the other hand, dysregulated miR-27a, 462 miR-421, 463 and lncRNA-PVT1 464 may be associated with HIF-1α-mediated cisplatin resistance in GC. Other newly identified HIF-1α-regulating downstream molecules that are closely related to GC EMT and metastasis include N-myc downstream-regulated gene 2 (NDRG2), 465 CXCR4, 466 liver X receptor α (LXRα), 467 and RhoE. ...
Gastric cancer (GC) ranks fifth in global cancer diagnosis and fourth in cancer-related death. Despite tremendous progress in diagnosis and therapeutic strategies and significant improvements in patient survival, the low malignancy stage is relatively asymptomatic and many GC cases are diagnosed at advanced stages, which leads to unsatisfactory prognosis and high recurrence rates. With the recent advances in genome analysis, biomarkers have been identified that have clinical importance for GC diagnosis, treatment, and prognosis. Modern molecular classifications have uncovered the vital roles that signaling pathways, including EGFR/HER2, p53, PI3K, immune checkpoint pathways, and cell adhesion signaling molecules, play in GC tumorigenesis, progression, metastasis, and therapeutic responsiveness. These biomarkers and molecular classifications open the way for more precise diagnoses and treatments for GC patients. Nevertheless, the relative significance, temporal activation, interaction with GC risk factors, and crosstalk between these signaling pathways in GC are not well understood. Here, we review the regulatory roles of signaling pathways in GC potential biomarkers, and therapeutic targets with an emphasis on recent discoveries. Current therapies, including signaling-based and immunotherapies exploited in the past decade, and the development of treatment for GC, particularly the challenges in developing precision medications, are discussed. These advances provide a direction for the integration of clinical, molecular, and genomic profiles to improve GC diagnosis and treatments.
... 286 HIF-1α stimulates multidrug resistance in GC cells through stimulating the transcription of miR-27a. 287 HIF-1α-induced miRNA-421 promotes metastasis, inhibits apoptosis, and induces cisplatin resistance by targeting E-cadherin and caspase-3 in GC. 288 Liu et al. suggested that HIF-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic GC cells. 48 Hypoxia increases the migration and invasion of GC cell line BGC-823 by activating HIF-1α and inhibiting N-myc downregulated gene 2 (NDRG2)-associated signaling pathway. ...
Molecular oxygen (O2) is essential for most biological reactions in mammalian cells. When the intracellular oxygen content decreases, it is called hypoxia. The process of hypoxia is linked to several biological processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, and other stress responses. The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia. Hypoxia-inducible factors (HIFs) sense hypoxia to regulate the expressions of a series of downstream genes expression, which participate in multiple processes including cell metabolism, cell growth/death, cell proliferation, glycolysis, immune response, microbe infection, tumorigenesis, and metastasis. Importantly, hypoxia signaling also interacts with other cellular pathways, such as phosphoinositide 3-kinase (PI3K)- mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) signaling, and endoplasmic reticulum (ER) stress. This paper systematically reviews the mechanisms of hypoxia signaling activation, the control of HIF signaling, and the function of HIF signaling in human health and diseases. In addition, the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted, which would provide novel strategies for the design and development of therapeutic drugs.
... The identified miRNAs were also confirmed as components of the RISC components. Previous reports have indicated that HIF-1 governs the expression of several miRNAs during hypoxia including miR-210, 67 miR-146a, 68 miR-145, 69 miR-382, 70 miR-191, 71 miR-363, 72 miR-421, 73 miR-204, 74 miR-30a, miR-21, 75,76 miR-687, 77 miR-155, 15 and miR-429 13 and miR-19a, 78 whereas to the best to our knowledge this is the first study identifying HIF-1 and HIF-2 specific, and HIF-2 specific miRNAs. ...
The cellular adaptive response to hypoxia relies on the expression of hypoxia‐inducible factors (HIFs), HIF‐1 and HIF‐2. HIFs regulate global gene expression changes during hypoxia that are necessary for restoring oxygen homeostasis and promoting cell survival. In the early stages of hypoxia, HIF‐1 is elevated, whereas at the later stages, HIF‐2 becomes the predominant form. What governs the transition between the two HIFs (the HIF switch) and the role of miRNAs in this regulation are not completely clear. Genome‐wide expression studies on the miRNA content of RNA‐induced silencing complexes (RISC) in HUVECs exposed to hypoxia compared to the global miRNA‐Seq analysis revealed very specific differences between these two populations. We analyzed the miRNA and mRNA composition of RISC at 2 h (mainly HIF‐1 driven), 8 h (HIF‐1 and HIF‐2 elevated), and 16 h (mainly HIF‐2 driven) in a gene ontology context. This allowed for determining the direct impact of the miRNAs in modulating the cellular signaling pathways involved in the hypoxic adaptive response. Our results indicate that the miRNA‐mRNA RISC components control the adaptive responses, and this does not always rely on the miRNA transcriptional elevations during hypoxia. Furthermore, we demonstrate that the hypoxic levels of the vast majority of HIF‐1‐dependent miRNAs (including miR‐210‐3p) are also HIF‐2 dependent and that HIF‐2 governs the expression of 11 specific miRNAs. In summary, the switch from HIF‐1 to HIF‐2 during hypoxia provides an important level of miRNA‐driven control in the adaptive pathways in endothelial cells.
... For example, ZEB1, which is targeted by the miR-200 family, regulates epithelial to mesenchymal transition in BRCA [32], and FERMT2-miR-200b pair has been associated with invasion in breast cancer [32,33]. Additionally, miRNAs like miR-182, miR-183, miR-21 are known to be associated with tumorigenesis [34][35][36]. ...
Recent research provides insight into the ability of miRNA to regulate various pathways in several cancer types. Despite their involvement in the regulation of the mRNA via targeting the 3′UTR, there are relatively few studies examining the changes in these regulatory mechanisms specific to single cancer types or shared between different cancer types.
We analyzed samples where both miRNA and mRNA expression had been measured and performed a thorough correlation analysis on 7494 experimentally validated human miRNA-mRNA target-gene pairs in both healthy and tumoral samples.
We show how more than 90% of these miRNA-mRNA interactions show a loss of regulation in the tumoral samples compared with their healthy counterparts.
As expected, we found shared miRNA-mRNA dysregulated pairs among different tumors of the same tissue. However, anatomically different cancers also share multiple dysregulated interactions, suggesting that some cancer-related mechanisms are not tumor-specific. 2865 unique miRNA-mRNA pairs were identified across 13 cancer types, ≈ 40% of these pairs showed a loss of correlation in the tumoral samples in at least 2 out of the 13 analyzed cancers. Specifically, miR-200 family, miR-155 and miR-1 were identified, based on the computational analysis described below, as the miRNAs that potentially lose the highest number of interactions across different samples (only literature-based interactions were used for this analysis).
Moreover, the miR-34a/ALDH2 and miR-9/MTHFD2 pairs show a switch in their correlation between healthy and tumor kidney samples suggesting a possible change in the regulation exerted by the miRNAs. Interestingly, the expression of these mRNAs is also associated with the overall survival. The disruption of miRNA regulation on its target, therefore, suggests the possible involvement of these pairs in cell malignant functions.
The analysis reported here shows how the regulation of miRNA-mRNA interactions strongly differs between healthy and tumoral cells, based on the strong correlation variation between miRNA and its target that we obtained by analyzing the expression data of healthy and tumor tissue in highly reliable miRNA-target pairs. Finally, a go term enrichment analysis shows that the critical pairs identified are involved in cellular adhesion, proliferation, and migration.
... The transcriptional regulation of human and mouse FST genes has been widely investigated, and many transcription factors have been identified to regulate FST gene. For example, erythroid 2 related factor (Nrf2) directly regulates FST gene and inhibits the apoptosis of human lung epithelial cells and A549 cells (Lin et al., 2016). It has been shown that transcription of FST gene is directly regulated by β-catenin/transcription factor 4 (TCF4) transcription factor complex to promote the murid myogenic differentiation and myoblast fusion in vitro and in vivo (Han et al., 2014). ...
... mRNAs and miRNAs are involved in many biological processes in animals, and not surprisingly, transcriptional analyses have revealed the differential expression of hypoxia regulators that enable adaptation to a hypoxic environment (Ni and Leng, 2016). The hypoxia-inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF), and mitogen-activated protein kinase (MAPK) signaling pathways are typical hypoxia-associated pathways (Lee et al., 2016;Zhang et al., 2018;Nicolas et al., 2019), and some mRNAs (PHD2, VHL, and FIH-1) and miRNAs (miR-363, miR-421, and miR-204) have been implicated in the regulation of the HIF-1 signaling pathway (Semenza, 2007;Ge et al., 2016;Wang et al., 2016;Xie et al., 2016). Studies of the molecular mechanisms of livestock adaptation to high altitude have focused on miRNA-mRNA interaction networks. ...
In the livestock production system, comprehending animal health and production is increasingly necessary to meet the global food demands. The production of animals with desired traits is, therefore, a prerequisite. To meet future food requirements, the strategy targets vertical growth (increasing productivity) rather than expanding the livestock population. Improving productivity requires a better understanding of genes and genomes, and consequently, their influence on the trait
of interest (i.e., production, reproduction, health and disease, or any other relevant traits in livestock), so that appropriate selection and breeding decisions can be implemented to improve livestock performance. Over the past decade,much biological research has focused on gene expression and regulation by noncoding RNAs (ncRNAs), variants, cis- or distal regulatory elements (transcription factors, enhancers and silencers), histone modifications, and DNA methylation. Advancement in high-throughput technologies
and cost reduction has enabled multi-omics studies to be performed on a large scale. Therefore, the crosstalk between multiple molecular layers is assessed by a systems biology approach that provides a systematic view of the regulatory mechanisms underlying complex traits. This approach proves beneficial for production systems (e.g., optimize animal nutrition, meat quality, or animal management) by selecting
the desirable animals and integrating accurate breeding programs or innovative management systems. For this research topic, we sought high-quality research papers describing novel insights into genetic and environmental factors that impact the mechanism and expression of production, reproduction and disease traits in livestock research. Research topics included the novel studies on the expression of genes,
micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), proteins and methylome for the trait of interest in livestock. The final research topic has 12 articles covering the aforementioned aspects in bovine, ovine, caprine, porcine and poultry populations. The quest for ideal therapeutic targets and biomarkers in disease traits in bovines has been riddled with many obstacles stemming from the molecular complexity of the disease and co-morbidities. Advances in omics technologies and the resulting amount of available data encompassing transcriptomics have created
an opportunity to integrate omics datasets to identify molecular changes and represent data through networks in disease traits such as bovine respiratory disease (BRD) and mastitis. Hasankhani et al., identified key modules and potential hub genes from transcriptome data using co-expression networks that underlie BRD. With two different approaches of module–trait relationships andmodule preservation analysis, the authors identified eight candidate modules and 307 hub-genes involved in the immune
response and BRD pathogenesis (Hasankhani et al.). Using a similar approach, Ghahramani et al., identified candidate genes and modules associated with mastitis in dairy cattle. Furthermore, they identified 360meta genes within twomodules by integratingmicroarray and RNA-Seq data. Additionally, the authors used attribute weighting and machine-learning methods to optimize predictive models using
hub genes that were informative in Escherichia coli mastitis (Ghahramani et al.). These studies utilized asystem’s level approach to provide a complete understanding of
complex biological systems of BRD and mastitis beyond the molecular level in cattle.
Even though omics technologies reveal global changes in RNA modifications under various conditions, researchers also focused on diverse functions of specific RNAs, particularly ncRNAs and circRNAs, due to their potential in regulating gene expression.
The ncRNAs are classified into several sub-classes, such as small non-coding RNAs, including miRNAs, small interfering RNAs, and lncRNAs, to name a few. Although lncRNAs biochemically resemble messenger RNAs (mRNAs), they do not template protein synthesis. Advances in computational biology and the evolution of sensitive RNA sequencing have facilitated the discovery of numerous lncRNAs and encouraged the study of their roles in livestock. An interesting study reported within this
research topic involved the regulatory role of lncRNA in the
transcriptome of abomasal lymph node tissue samples from adult
Spanish Churra sheep after experimental infection with the
gastrointestinal nematode Teladorsagia circumcincta (Chitneedi
et al.). The authors identified ten differentially expressed
lncRNAs between samples from animals that differ in
infection resistance associated with signaling pathways like
cellular growth, proliferation and development, cellular stress
and injury, intracellular and second messenger signaling and
apoptosis (Chitneedi et al.). In a separate study on sheep hair
follicle development and morphogenesis, Xu et al., identified the
STAT3 gene partially inhibiting cell proliferation via direct
negative regulation of FST gene expression.
miRNAs are small and highly conserved non-coding RNA
molecules that orchestrate various biological processes through
post-transcriptional expression regulation. A study by Kusama
et al., aimed to characterize proteins and exosomal miRNAs in the
uterine flushing of pregnant and non-pregnant cows after
artificial insemination. The authors identified 336 proteins, of
which 260 were more than two-fold higher in pregnant cows. The
authors identified SUGT1 as the best predictor for the presence of
embryos in the uterus that altered protein composition and
exosomal miRNA contents in the uterine fluid (Kusama et al.).
In an independent miRNA study in cattle, bta-miR-150 was
found to have a negative regulatory effect on the
differentiation of bovine adipocytes and promoted
proliferation, inhibited adipocyte differentiation, and reduced
lipid droplet formation (Chen et al.). The research clarified the
relationship between bta-miR-150 and adipocyte differentiation
in cattle. Differentiation of intramuscular preadipocytes was also
inhibited by overexpression of KLF4 by targeting C/EBPβ in goats
(Xu et al.). Since the adipose tissue in meat impacts the economic
value of animals, these studies focusing on the molecular
mechanisms underlying adipose tissue generation were
primarily crucial for the beef production industry. As beef
producers continue to improve efficiency, another crucial
aspect of skeletal muscle mass impacts consumer acceptance
of meat products. Sheng et al., used the proteomics approach
to unravel the mechanism of myostatin in regulating cattle
skeletal development.
... He et al. (2017) indicated up-regulation of miR-25 was essential for GC cells to establish a cisplatin-resistant phenotype through a FOXO3a-dependent mechanism. Ge et al. (2016) investigated the roles of miR-421, a HIF-1α induced miRNA detected to be higher in advanced GC, and found that overexpression of miR-421 enhanced metastasis, suppressed apoptosis, and induced cisplatin resistance by targeting E-cadherin and caspase-3 in GC cells. It was demonstrated that Calpain1 and Calpain2, regulated by Calpain small subunit 1 (CAPNS1), were implicated in cisplatin resistance in GC by cleaving the downstream proteins caspase3 and PARP1 to induce apoptosis. ...
Platinum-based cytotoxic chemotherapy is considered the standard treatment for advanced gastric cancer (GC). However, cisplatin chemoresistance often occurs with the mechanisms being not well clarified, which results in the cancer recurrence and poor survival. Ginsenoside Rg3, isolated from the Chinese Herb Panax Ginseng, is recognized as an anti-cancer agent. Herein, we aimed to reveal whether Ginsenoside Rg3 alleviates cisplatin resistance and sensitizes GC cells to cisplatin-induced apoptosis, and draw out the underlying molecular mechanism in cisplatin-resistant GC cells. The lower expression of miR-429 was found in AGSR-CDDP cells; it was also in association with cisplatin-resistance in GC cells and expression of which was restored following Ginsenoside Rg3 treatment. We also demonstrated that miR-429 made a contribution toward chemosensitivity in GC cells partly through SOX2 regulation. SOX2 was found to contribute to developing platinum resistance and was an authentic target for miR-429 in AGSR-CDDP cells. Importantly, enforced expression of SOX2 with a pcDNA3-SOX2 construct lacking the 3′-UTR miRNA binding site diminished the cytotoxic effects of miR-429 in AGSR-CDDP cells. We demonstrated that Ginsenoside Rg3 enhanced chemosensitivity in AGSR-CDDP GC cells, at least in part, through up-regulating miR-429, thereby targeting SOX2 and modulating downstream PI3K/AKT/mTOR signaling. Ginsenoside Rg3 was also found to regulate apoptosis-related genes via miR-429 in cisplatin-resistant GC cells. Ginsenoside Rg3 treatment significantly suppressed the migration rate of AGSR-CDDP GC cells, while following transfection with anti-miR-429, the anti-migratory effects of Ginsenoside Rg3 was partially abolished. This data suggested that Ginsenoside Rg3 may impede the chemoresistance and migration of GC cells mainly mediated through miR-429. We concluded that miR-429-regulated SOX2 expression was one of the main mechanisms by which Ginsenoside Rg3 dramatically promoted its anticancer effects on cisplatin-resistant GC cells. We also underscored a supporting model in which miR-429 adjusted PI3K/AKT/mTOR signaling by regulating SOX2 in cisplatin-resistant GC cells.
