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Micro ribonucleic acid (miR)-451 was successfully upregulated in A549 cells by pre-miR-451 transfection. Relative expression levels of miR-451 in A549 cells were measured at 24, 48, and 72 hours after transient transfection with pre-miR-451 by real-time quantitative polymerase chain reaction. RNU6 served as an endogenous control. Each value represents the mean ± standard deviation of three independent experiments. *P < 0.05 versus cells transfected with scrambled control.
Source publication
Background:
As radioresistance of non-small cell lung cancers (NSCLC) is one of the main causes of failure in radiotherapy, we examined whether micro ribonucleic acid (miR-451) could function as a potential radiosensitizer of NSCLC and the related mechanism.
Methods:
Radioresistant NSCLC cell line A549 was transfected with pre-miR-451 or a scram...
Context in source publication
Context 1
... performed RT-PCR analysis of miR-451 expression in NSCLC A549 cells transfected with pre-miR-451 or a scrambled control to validate transfection efficiency. As shown in Figure 1, the relative expression level of miR-451 was significantly higher in pre-miR-451-transfected A549 cells compared with those transfected with the scrambled control (P < 0.05). Even at 72 hours after transfection, there was still about 30-fold induction. ...
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Objective:
Stem-cell therapy is a promising treatment for cartilage defects. The newly identified urine-derived stem cells (USCs), which have multipotency and sufficient proliferative ability, are promising candidates for several tissue engineering therapies. In this study, we investigated the role of USC extracellular vehicles (EVs) in promoting...
Citations
... Increased expression of miR-451 sensitizes NSCLC A549 radiation-resistant cells by increasing apoptosis. Activation of PTEN after irradiation may be associated with A549 cell radiation sensitivity due to overexpression of miR-451 [155]. Functionally, miR-9-transfected A549 cells by targeting Neuropilin 1 (NRP1) showed weaker migratory and invasive abilities, reduced proliferation, and increased apoptosis. ...
Resistance to cancer radiotherapy is one of the biggest concerns for success in treating and preventing recurrent disease. Malignant tumors may develop when they block genetic mutations associated with apoptosis or abnormal expression of apoptosis; Tumor treatment may induce the expression of apoptosis-related genes to promote tumor cell apoptosis. MicroRNAs have been shown to contribute to forecasting prognosis, distinguishing between cancer subtypes, and affecting treatment outcomes in cancer. Constraining these miRNAs may be an attractive treatment strategy to help overcome radiation resistance. The delivery of these future treatments is still challenging due to the excess downstream targets that each miRNA can control. Understanding the role of miRNAs brings us one step closer to attaining patient treatment and improving patient outcomes. This review summarized the current information on the role of microRNA-induced apoptosis in determining the radiosensitivity of various cancers.
... Studies in non-small cell lung cancer (NSCLC) have demonstrated the tumor inhibitory role of miR-451. The upregulation of miR-451 inhibited the growth of NSCLC cell line A549 and enhanced its apoptosis 11,12 . MicroRNA-451 is used as a prognostic marker for the diagnosis of thyroid papillary carcinoma and lymph node metastasis 13 . ...
Objective:
Long non-coding RNA (lncRNA) NORAD plays an essential role in the development and progress of papillary thyroid carcinoma (PTC). MicroRNA-451 (MiR-451) has been identified as playing an inhibitory role in some types of cancer. However, the molecular mechanism of lncRNA NORAD regulating metastasis of PTC cells by miR-451 has not been fully elucidated.
Materials and methods:
Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) or Western blot analysis of the expression of NORAD, miR-451, and interleukin-6 receptor (IL-6R) in PTC cell lines were carried out. The detection of Luciferase reporter gene showed the relationship between lncRNA NORAD, miR-451 and IL-6R. Cell Counting Kit-8 (CCK-8) assay and transwell assay were performed to detect the influence of lncRNA NORAD, miR-451 on the proliferation, migration, and invasion of PTC cells.
Results:
The results of RT-qPCR and Western blotting suggested that the expression of lncRNA NORAD and IL-6R were higher than that of the control group, while the expression of miR-451 was lower. Transwell assay indicated that the knockdown of lncRNA NORAD or overexpression of miR-451 significantly inhibited cell proliferation, migration and invasion in PTC cell lines. In addition, lncRNA NORAD negatively controls the expression of miR-451, resulting in the upregulation of IL-6R. IL-6R overexpression can reverse the inhibitory effect of lncRNA NORAD knockdown or miR-451 on PTC cell proliferation and metastasis.
Conclusions:
Our results indicated that the cell migration and invasion were inhibited by knockdown of lncRNA NORAD or overexpression of miR-451, suggesting that the axis of lncRNA NORAD -miR-451- IL-6R was involved in the development of PTC.
... Increased expression of miR-451 amplifies the sensitivity of A549 cells in response to DDP chemo-sensitivity through apoptosis [27]. Moreover, miR-451 expression can enhance the sensitivity of cancer cells to radiotherapy by increasing the level of phosphatase, tensin homolog (PTEN) protein, and activating apoptosis [31]. Studies show that the over-expression of miR-451 in A549 cells reduces the expression of lung cancer metastatic agents such as MMP-2, MMP-9, VEGF, and CXCR4 and decreases the expression of inflammatory factors. ...
... They found that the increased expression of miR-451 sensitized A549 cells to radiation by increasing apoptosis. Following radiation exposure, the PTEN factor is activated, and by increasing the expression of miR-451, A549 cells become sensitive to radiation [31]. ...
MicroRNAs (miRNAs) are highly conserved non-coding RNAs involved in many physiological processes such as cell proliferation, inhibition, development of apoptosis, differentiation, suppresses tumorigenicity, and regulating cell growth. The description of the alterations of miRNA expression patterns in cancers will be helpful to recognize biomarkers for early detection and possible therapeutic intervention in the treatment of cancers. Recent studies have shown that miR-451 is broadly dysregulated in lung cancer and is a crucial agent in lung tumor progression. This review summarizes recent advances of the potential role of miR-451 in lung cancer diagnosis, prognosis, and treatment and provides an insight into the potential use of miR-451 for the development of advanced therapeutic methods in lung cancer.
... Wang et al. reported that miRNA-451 is the most downregulated miRNA in NSCLC tissues, and acts as a tumor inhibitor in NSCLC by targeting ras-related protein 14. Tian et al. found that miRNA-451 could promote the PTEN protein level in NSCLC cells, leading to increased radiotherapy sensitivity of NSCLC cells (43). Liu et al. confirmed that MIF was a target of miRNA-451 and reduced the proliferation activity, colony formation ability, and migration and invasion of nasopharyngeal carcinoma cells (44). ...
... Proliferation 2016 miRNA-182 Recent studies have found that miRNA-182 is significantly up-regulated in a variety of solid tumors and may be a carcinogen(41) 2018miRNA-338 The low expression of miRNA-338 was associated with the tumor and its recurrence, suggesting that miRNA-338 may be negatively correlated with the metastasis of 451 miRNA-451 plays a role as a tumor inhibitor in NSCLC by targeting RAS-related protein 14 (RABl4), and research results show that the low expression of miRNA-451 is associated with lymph node metastasis in NSCLC patients, and the high expression of miRNA-451 has a poor prognosis in NSCLC patients(43)(44)(45)(46) 2013, 2014 miRNA-218 miRNA-218 is associated with the proliferation and migration of tumor cells(47,48) 2019 miRNA-448 miRNA-448 inhibits the proliferation and migration of tumor cells(49) ...
The liver is one of the most common sites of metastatic spread of lung cancer, and the process of metastasis is regulated by many factors. A number of genes, including multiple tumor suppressor 1 (mts1), p120 catenin, and CT45A1, increase the possibility of hepatic metastasis in lung cancer, whereas Tip30/ CC3, CUL5, and SOCS3 expression in lung tumors inhibit tumor metastasis. microRNAs (miRNAs), such as miRNA-126, miRNA-338, and miRNA-218, can affect the metastasis of lung cancer cells to the liver. The D114-Notch signaling pathway can inhibit liver metastasis in small cell lung cancer. Serum tumor markers cytokeratin 19 fragment antigen 21-1 and neuron-specific enolase (NSE) are closely related to the risk of hepatic metastasis in lung cancer. Based on previously published literature, we found that the metastasis and invasion of lung cancer to the liver are determined by molecular factors. Therefore, the selective identification and intervention of these erroneous signals can predict early lung cancer metastasis to the liver. In this review article, we describe the mechanisms and influencing factors (genes, signal pathways, chemicals, proteins, miRNAs) of hepatic metastasis in lung cancer. We hope to provide a summary of the evidence for the mechanisms by which related genes or proteins affect the malignancy of liver metastasis from lung cancer so that doctors and researchers can improve treatment options.
... A current literature search reveals an association between the expression of these miRNAs, their targets (e.g., Chk1, c-Myc, ATM and Cyclins) and either radioresistance or radiosensitivity (Table 2) [98,107,113,120]. Most of these miRNAs (miR-15b, miR-451, miR-186, miR-421, miR-98, miR-142, miR-26b, miR-16, let-7 family) mediate radiosensitivity [98,[105][106][107][108][109][112][113][114][116][117][118]120,121] suggesting that the radiation-induced downregulation of these miRNAs might enhance radioresistance. ...
Simple Summary
Pancreatic cancer is an aggressive disease with a high mortality rate. Radiotherapy is one treatment option within a multimodal therapy approach for patients with locally advanced, non-resectable pancreatic tumors. However, radiotherapy is only effective in about one-third of the patients. Therefore, biomarkers that can predict the response to radiotherapy are of utmost importance. Recently, microRNAs, small non-coding RNAs regulating gene expression, have come into focus as there is growing evidence that microRNAs could serve as diagnostic, predictive and prognostic biomarkers in various cancer entities, including pancreatic cancer. Moreover, their high stability in body fluids such as serum and plasma render them attractive candidates for non-invasive biomarkers. This article describes the role of microRNAs as suitable blood biomarkers and outlines an overview of radiation-induced microRNAs changes and the association with radioresistance in pancreatic cancer.
Abstract
Today, pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with a five-year overall survival rate of less than 7%. Only 15–20% of patients are eligible for curative intent surgery at the time of diagnosis. Therefore, neoadjuvant treatment regimens have been introduced in order to downsize the tumor by chemotherapy and radiotherapy. To further increase the efficacy of radiotherapy, novel molecular biomarkers are urgently needed to define the subgroup of pancreatic cancer patients who would benefit most from radiotherapy. MicroRNAs (miRNAs) could have the potential to serve as novel predictive and prognostic biomarkers in patients with pancreatic cancer. In the present article, the role of miRNAs as blood biomarkers, which are associated with either radioresistance or radiation-induced changes of miRNAs in pancreatic cancer, is discussed. Furthermore, the manuscript provides own data of miRNAs identified in a pancreatic cancer mouse model as well as radiation-induced miRNA changes in the plasma of tumor-bearing mice.
... An overexpression of the cluster confers radioresistance to lymphoma cells [37]. On the contrary, radiosensitizing effects were described for miR-451a in lung cancer [38,39]. Considering the radiation-increased levels of miR-155-3p, miR-20a-5p and miR-17 together with the decreased amount of miR-451a, EVs from irradiated donors have the potential to transport prosurvival signals. ...
Normal tissue toxicity is a dose-limiting factor in radiation therapy. Therefore, a detailed understanding of the normal tissue response to radiation is necessary to predict the risk of normal tissue toxicity and to development strategies for tissue protection. One component of normal tissue that is continuously exposed during therapeutic irradiation is the circulating population of peripheral blood mononuclear cells (PBMC). PBMCs are highly sensitive to ionizing radiation (IR); however, little is known about how IR affects the PBMC response on a systemic level. It was the aim of this study to investigate whether IR was capable to induce changes in the composition and function of extracellular vesicles (EVs) secreted from PBMCs after radiation exposure to different doses. Therefore, whole blood samples from healthy donors were exposed to X-ray radiation in the clinically relevant doses of 0, 0.1, 2 or 6 Gy and PBMC-secreted EVs were isolated 72 h later. Proteome and miRNome analysis of EVs as well as functional studies were performed. Secreted EVs showed a dose-dependent increase in the number of significantly deregulated proteins and microRNAs. For both, proteome and microRNA data, principal component analysis showed a dose-dependent separation of control and exposed groups. Integrated pathway analysis of the radiation-regulated EV proteins and microRNAs consistently predicted an association of deregulated molecules with apoptosis, cell death and survival. Functional studies identified endothelial cells as an efficient EV recipient system, in which irradiation of recipient cells further increased the uptake. Furthermore an apoptosis suppressive effect of EVs from irradiated PBMCs in endothelial recipient cells was detected. In summary, this study demonstrates that IR modifies the communication between PBMCs and endothelial cells. EVs from irradiated PBMC donors were identified as transmitters of protective signals to irradiated endothelial cells. Thus, these data may lead to the discovery of biomarker candidates for radiation dosimetry and even more importantly, they suggest EVs as a novel systemic communication pathway between irradiated normal, non-cancer tissues.
... miR451 overexpression has been reported to activate PTEN posttranscriptionally after irradiation, amplify suppressive impact, and facilitate A549-cell radiosensitization. 47 As a key downstream component of the PI3K-Akt pathway, mTOR is directly mediated by miR99a. miR99a expression is significantly upregulated in RT-sensitive cells, while mTOR overexpression inversely diminishes cell apoptosis and exacerbates radioresistance. ...
Lung cancer is the most prevalent and deadly malignancy. Radiotherapy is a major treatment modality for lung cancer. Nevertheless, radioresistance poses a daunting challenge that largely limits the efficacy of radiotherapy. There is a pressing need for deciphering molecular mechanisms underlying radioresistance and elucidating novel therapeutic targets for individualized radiotherapy. MicroRNAs are categorized as small noncoding RNAs that modulate target-gene expression posttranscriptionally and are implicated in carcinogenesis and cancer resistance to treatment. Overwhelming evidence has unraveled that tissue-specific miRNAs are essential for regulation of the radiosensitivity in lung cancer cells through a complex interaction with multiple biological processes and radiation-induced pathways. Moreover, exosome-derived miRNAs are a novel horizon in lung cancer treatment in which exosomal miRNAs act as potential diagnostic and therapeutic biomarkers of radiotherapy. In the present review, we discuss the mediation of key biological processes and signaling pathways by tissue-specific miRNAs in lung cancer radiotherapy. Additionally, we provide new insight into the potential significance of exosomal miRNAs in radiation response. Lastly, we highlight miRNAs as promising predictors and therapeutic targets to tailor personalized lung cancer radiotherapy.
... MiR-130 might regulate PTEN expression through different ways according to the cellular context. PTEN protein was found to be slightly increased after the pre-miR-451-transfection in lung cancer cells [60]. Both miR-451 and PTEN expression level was reported to be significantly reduced in ovarian cancer [61]. ...
Abstract Phosphatase and tensin homologue (PTEN) triggers a battery of intracellular signaling pathways, especially PI3K/Akt, playing important roles in the pathogenesis of multiple diseases, such as cancer, neurodevelopmental disorders, cardiovascular dysfunction and so on. Therefore PTEN might be a biomarker for various diseases, and targeting the abnormal expression level of PTEN is anticipated to offer novel therapeutic avenues. Recently, noncoding RNAs (ncRNAs) have been reported to regulate protein expression, and it is definite that PTEN expression is controlled by ncRNAs epigenetically or posttranscriptionally as well. Herein, we provide a review on current understandings of the regulation of PTEN by ncRNAs, which could contribute to the development of novel approaches to the diseases with abnormal expression of PTEN.
... 9 Emerging evidences have revealed the potential role of miR-451 in NSCLC progression and prognosis, as well as in drug resistance. 10,11 Recent years, many researchers have focus on the interplay between lncRNA and microRNA (miRNA), as well as the important of such interaction in tumorigenesis. A well-accepted hypothesis suggested that lncRNA could sever as a competing endogenous RNA (ceRNA) of miRNA to modulate the expression of cancer-related target gene. ...
Background: Chemoresistance has been considered to be a major obstacle for cancer therapy clinically. Long non-coding RNAs (LncRNAs) are asscociated with the development, prognosis and drug-resistance of non-small cell lung cancer (NSCLC). Whereas, the regulatory mechanism of lncRNA TATDN1 in the cisplatin resistance of NSCLC is still not clear.
Methods: The expression of TATDN1, miR-451 and TRIM66 in NSCLC tissues and cell lines were detected by qRT-PCR or western blot. Immunohistochemistry (IHC) assay was performed for the detection of TATDN1 expression profile. 88 patients who underwent cisplatin treatment were followed up to 60-months for the analysis of survival rate. MTT and Flow cytometry analysis were performed for the assessment of cell survival rate, proliferation and apoptosis. Bioinformatics, Dual-Luciferase reporter were employed to analyze the interaction among TATDN1, miR-451 and TRIM66. Xenograft tumor model was constructed to verify the role of TATDN1 in NSCLC treated with cisplatin (DDP) in vivo.
Results: TATDN1 and TRIM66 was significantly upregulated while miR-451 was downregulated in NSCLC tissues and cell lines, especially in DDP-resistant tumor tissues and cells. Survival rates of NSCLC patients with low TATDN1 expression were improved following DDP chemotherapy. TATDN1 upregulated TRIM66 expression via sponge for miR-451. Moreover, TATDN1 knockdown improved DDP-sensitivity in NSCLC patients by regulation of miR-451/TRIM66 axis. Finally, knockdown of TATDN1 improved the sensitivity of NSCLC to DDP in vivo.
Conclusions: TATDN1 enhanced the DDP-tolerance of NSCLC cells by upregulating TRIM66 expression via sponging miR-451, hinting a novel regulatory pathway of chemoresistance in DDP-tolerant NSCLC cells and providing a potential therapeutic target for NSCLC patients with DDP-reistance.
... Accumulating evidence showed that miR-451 plays a key role in different aspects of carcinogenesis in lung cancer anti-invasive effects of delta-tocoterienol in nsclc including tumor growth, invasion, radioresistance, and chemoresistance. [38][39][40][41] A recent case analysis with 370 NSCLC incidents revealed that miR-451 expression was lower in carcinoma tissues than in paired background lung tissues. 42 The same study also revealed that the miR-451 expression was inversely correlated with macrophage migration inhibitory factor expression, a factor that induces the expression of MMP-9. ...
