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HIF1A-AS2 regulates cell proliferation, cell cycle progression and invasion of osteosarcoma cells through the modulation of miR-129-5p. (A) The cell proliferation of MG-63 cells was determined by MTT analysis. (B) Ectopic expression of miR-129-5p decreased the S phase of HIF1A-AS2-overexpressing MG-63 cells compared to that of the scrambled group. (C) Elevated expression of miR-129-5p suppressed the invasion of HIF1A-AS2-overexpressing MG-63 cells compared to the invasion of the scrambled group. (D) The relative invasive cells are shown. *p<0.05, **p<0.01 and ***p<0.001.
Source publication
Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) play vital roles in tumor development and progression. However, the relationship between osteosarcoma and HIF1AAS2 remains unknown. The expression of HIF1AAS2 and miR-129-5p was detected in osteosarcoma cell lines and samples via qRT-PCR. Cell Counting Kit-8 (CCK-8) and invasio...
Contexts in source publication
Context 1
... aimed to determine whether HIF1A-AS2 acted by silencing miR-129-5p expression. The MTT assay indicated that the miR-129-5p mimic could inhibit the promotion of proliferation induced by HIF1A-AS2 overexpression ( Figure 6A). Ectopic expression of miR-129-5p decreased the S phase of the HIF1A-AS2-overexpressing MG-63 cells compared to that of the scrambled group ( Figure 6B, p<0.05). ...
Context 2
... expression of miR-129-5p decreased the S phase of the HIF1A-AS2-overexpressing MG-63 cells compared to that of the scrambled group ( Figure 6B, p<0.05). In addition, elevated expression of miR-129-5p suppressed the invasion of HIF1A-AS2-overexpressing MG-63 cells compared to that of the scramble group ( Figure 6C and 6D, p<0.001). www.aging-us.com ...
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Background
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Citations
... Previous studies have demonstrated that HIF1A-As2 promotes cell proliferation and migration in a variety of cancers [16,[41][42][43]. HIF1A-As2 is also upregulated in lung cancer and is associated with poor outcomes [44,45]. ...
Lung cancer is the leading cause of cancer-related deaths worldwide. KRAS is the main oncogenic driver in lung cancer that can be activated by gene mutation or amplification, but whether long non-coding RNAs (lncRNAs) regulate its activation remains unknown. Through gain and loss of function approaches, we identified that lncRNA HIF1A-As2 , a KRAS-induced lncRNA, is required for cell proliferation, epithelial-mesenchymal transition (EMT) and tumor propagation in non-small cell lung cancer (NSCLC) in vitro and in vivo. Integrative analysis of HIF1A-As2 transcriptomic profiling reveals that HIF1A-As2 modulates gene expression in trans, particularly regulating transcriptional factor genes including MYC. Mechanistically, HIF1A-As2 epigenetically activates MYC by recruiting DHX9 on MYC promoter, consequently stimulating the transcription of MYC and its target genes. In addition, KRAS promotes HIF1A-As2 expression via the induction of MYC, suggesting HIF1A-As2 and MYC form a double-regulatory loop to strengthen cell proliferation and tumor metastasis in lung cancer. Inhibition of HIF1A-As2 by LNA GapmeR antisense oligonucleotides (ASO) significantly improves sensitization to 10058-F4 (a MYC-specific inhibitor) and cisplatin treatment in PDX and KRAS LSLG12D -driven lung tumors, respectively.
... Zheng and Lin (2021) found that lncRNA HCG18 promotes OS progression through miR-148b/ETV5 regulation; a transwell assay in OS cells after LncRNAHCG18 knockdown showed significantly suppressed migration and invasion. Wang et al. (2019) proposed that lncRNA HIF1A-AS2 overexpression promoted OS progression through the modulation of miR-129-5p. The authors used wound healing and invasion assays of OS cells measure determine cell proliferation and invasion ability and concluded that silencing lncRNA HIF1A-AS2 significantly decreased OS cell invasion and metastasis. ...
Osteosarcoma (OS) is one of the most common primary solid malignant tumors in orthopedics, and its main clinical treatments are surgery and chemotherapy. However, a wide surgical resection range, functional reconstruction of postoperative limbs, and chemotherapy resistance remain as challenges for patients and orthopedists. To address these problems, the discovery of new effective conservative treatments is important. Long non-coding RNAs (lncRNAs) are RNAs longer than 200 nucleotides in length that do not encode proteins. Researchers have recently found that long non-coding RNAs are closely associated with the development of OS, indicating their potentially vital role in new treatment methods for OS. This review presents new findings regarding the association of lncRNAs with OS and summarizes potential clinical applications of OS with lncRNAs, including the downregulation of oncogenic lncRNAs, upregulation of tumor suppressive lncRNAs, and lncRNAs-based treatment to improve chemotherapy resistance. We hope these potential methods will be translated into clinical applications and greatly reduce patient suffering.
... Previous studies have revealed that HIF1A-AS2 is a type of lncRNA that promote cancer progression, and its role has been reported in many cancer studies, such as osteosarcoma, 17 ovarian, 18 and gastric cancer. 19 Consistently, HIF1A-AS2 contributed to proliferation, metastasis, and tumorigenesis of LUAD cells, indicating that HIF1A-AS2 is a positive regulator in the development of LUAD. ...
Although epidermal growth factor receptor tyrosine kinase inhibitors show efficacy in lung adenocarcinoma patients, tyrosine kinase inhibitor resistance inevitably develops, limiting long-term results. Thus, there is an urgent need to address drug resistance in lung adenocarcinoma. LncRNA HIF1A-AS2 could be a critical mediator in the progression of various tumor types. We examined the function of HIF1A-AS2 in modifying tumor aggravation and osimertinib resistance in lung adenocarcinoma. Using clinical samples, we showed that HIF1A-AS2 was upregulated in lung adenocarcinoma specimens, predicting poorer overall survival and disease-free survival. HIF1A-AS2 silencing inhibited the proliferation, migration, and tumorigenesis of lung adenocarcinoma cells and therapeutic efficacy of osimertinib against tumor cells in vitro and in vivo. RNA precipitation assays, western blotting, luciferase assays, and rescue experiments demonstrated that HIF1A-AS2 sponged miR-146b-5p, promoting IL-6 expression, activating the IL-6/STAT3 pathway, and leading to lung adenocarcinoma progression. miR-146b-5p and IL-6 levels were correlated with the prognosis of lung adenocarcinoma patients. Our results indicated that HIF1A-AS2 functions as an oncogenic factor in adenocarcinoma cells by targeting the miR-146b-5p/IL-6/STAT3 axis and may be a prognostic indicator of survival. Moreover, it can be a potential therapeutic target to enhance the efficacy of osimertinib in lung adenocarcinoma patients.
... The lncRNA HIF1A-AS2 has also been shown to be upregulated in OS, and is associated with poor survival. HIF1A-AS2 regulates the tumorigenesis of OS, as demonstrated by its effects on cell proliferation, cell cycle progression and invasion, through 'sponging' miR-129-5p (69). In OS, the lncRNA TTN-AS1 has been shown to facilitate cell growth, apoptosis and drug resistance via the miR-134-5p/MBTD1 axis (70). ...
... By contrast, the lncRNA TTN-AS1 also acts as a ceRNA on miRNA-376a, enhancing the malignancy of OS via upregulating dickkopf-1 (71). Other confirmed lncRNAs are presented in Table II (68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79). ...
Osteosarcoma (OS) is the most common primary bone tumor worldwide. OS exhibits a range of aggressive behaviors, including early metastasis potential, rapid progression, poor clinical prognosis and insensitivity to chemoradiotherapy. Non‑coding RNAs are transcripts that do not encode proteins. A significant number of studies published on OS have been focused on the aberrant expression of non‑coding RNAs and their involvement in tumor initiation and progression. It has been confirmed that non‑coding RNAs exert their regulatory functions at both the transcriptional and post‑transcriptional level, which leads to tumor initiation or progression in OS. According to present knowledge, this review provides a state‑of‑the‑art overview of the functions and mechanisms of microRNAs, long non‑coding RNAs and circular RNAs in terms of their involvement with OS. The review also covers their potential clinical application in the diagnosis, prognosis and treatment of OS. It is hoped that the information presented in this review on the involvement of non‑coding RNAs in OS will lead to a more comprehensive understanding of OS and provide a useful perspective on the potential diagnostic and therapeutic applications of non‑coding RNAs for patients with OS.
... Mechanistically, HIF1A-AS2/miR-33b-5p/SIRT6 was confirmed to regulate OS cell proliferation, migration and apoptosis. Wang et al (40) also confirmed increased expression of HIF1A-AS2 in 30 OS samples and four OS cell lines compared with the adjacent normal tissues and osteoblast cell lines, respectively. Moreover, high HIF1A-AS2 expression was associated with poor survival rates. ...
... Wu et al (14) reported that HIF1A-AS2 functions as a protein decoy to inhibit the transcription of PHLDA1 by binding to LSD1, a histone demethylase. Additionally, HIF1A-AS2 acts as a molecular sponge to bind miRNAs to further affect expression of other genes (23,40,50,54,56). Although significant achievements have been obtained with regard to understanding the role of HIF1A-AS2 in various types of cancer, further studies are still required with regard to its regulatory function, as lncRNAs often exhibit several complex regulatory functions/mechanisms. ...
Long non-coding RNAs (lncRNAs) are transcripts that are >200 nucleotides, but with no open reading frame. An increasing number of lncRNAs have been identified following the development of second-generation sequencing technologies, and they have since become a research hotspot. Functionally, they play a vital role in tumor progression, including in tumor proliferation, migration, invasion, apoptosis and acquisition of drug resistance. They regulate gene expression primarily through interaction with DNA, RNA and proteins at the epigenetic, transcriptional and post-transcriptional levels. Endogenous hypoxia-inducible factor 1α antisense RNA 2 (lncRNA HIF1A-AS2) is aberrantly expressed and involved the development/progression of various types of tumors, such as bladder cancer, glioblastoma, breast cancer and osteosarcoma. It plays a vital role in the proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transformation of various tumor cells. This review summarizes the current body of knowledge on the biological functions and related molecular mechanisms of lncRNA HIF1A-AS2 in the development/progression of human tumors and other diseases.
... The high-dose chemotherapy was introduced about 35 years ago, while the OS survival rate has not improved since then [3]. Mounting researches have proved that long non-coding RNA (lncRNA) exerts a crucial effect in tumor occurrence and growth [4]. Therefore, the study of the molecular mechanism in OS is expected to provide a new therapeutic strategy. ...
Background
Long non-coding RNA (lncRNA) RUSC1-AS1 has been found to modulate several cancers development. In this study, we explored the role of RUSC1-AS1 on osteosarcoma (OS) progression.
Methods
Quantitative Real-time PCR (qRT-PCR) was conducted to test the relative expression of RUSC1-AS1, Notch1 mRNA and miR-101-3p in OS tissues and adjacent normal tissues. Gain- or loss- of functional assays were carried out to determine the roles of RUSC1-AS1 and miR-101-3p in OS progression both in vitro and in vivo. The expression of E-cadherin, N-cadherin, Vimentin, Snail, Notch1, Ras and ERK was determined by Western blot. Furthermore, the relationships between RUSC1-AS1 and miR-101-3p, Notch1 and miR-101-3p were confirmed through RNA immunoprecipitation (RIP) and dual luciferase reporter gene assay.
Results
RUSC1-AS1 and Notch1 were up-regulated in OS cells and tissues. Down-regulating RUSC1-AS1 significantly attenuated the proliferative, epithelial-mesenchymal transition (EMT), growth, lung metastasis, migrative and invasive abilities of MG-63 and Saos-2 cells, and aggravated apoptosis, accompanied with down-regulated Notch1-Ras-ERK1/2 in those cells both in vitro and in vivo, while overexpression of RUSC1-AS1 exerted opposite effects. Overexpressing miR-101-3p in OS cells had similar effects as RUSC1-AS1 inhibition. In addition, RUSC1-AS1 functioned as a competing endogenous RNA (ceRNA) to competitively sponge miR-101-3p, thus upregulating Notch1 expression and mediating the malignant behaviors of OS cells.
Conclusion
RUSC1-AS1 is a novel oncogenic lncRNA in OS through the miR-101-3p-Notch1-Ras-ERK pathway, which might be a potential therapeutic target for OS.
... The biogenesis of mature miR-129 undergoes the following stages: Pri-miR-129 (the non-coding primary transcript of the miR-129 gene transcribed by RNA polymerase II), pre-miR-129 (the 70-nucleotide stem-loop precursor miR-129 obtained by cleaving pri-miR-129 through Drosha ribonuclease III enzyme), duplex (the complex composed of mature miRNA and antisense miRNA, and obtained by cleaving pre-miR-129 by the cytoplasmic Dicer ribonuclease) and the mature miR-129 strand (one of the strands from the duplex that will be incorporated into Argonaute and then into the RNA-induced silencing complex) (3). It has been reported that the expression of the miR-129 family is aberrant in several types of oncological and non-oncological diseases; it is downregulated in prostate cancer (miR-129-5p and miR-129-3p) (4), osteosarcoma (miR-129-5p) (5), lung cancer (miR-129-5p) (6), breast cancer (miR-129-5p) (7), nasopharyngeal carcinoma (miR-129-5p) (8), ovarian cancer (miR-129-5p and miR-129-3p) (9), colon cancer (miR-129-5p and miR-129-3p) (10), heart failure (HF; miR-129-5p) (11), epilepsy (miR-129-5p) (12), intervertebral disc degeneration (IVDD; miR-129-5p) (13) and Alzheimer's disease (AD; miR-129-5p) (14), but upregulated in obesity (miR-129-5p and miR-129-3p) (15) and diabetes (miR-129-5p and miR-129-3p) (16). In different diseases, the miR-129 family has different targets for modulating various biological processes (Tables I and II) and involves multiple signaling pathways (Figs. 1 and 2), thus playing an important role in promoting or blocking disease progression (Tables III and IV). ...
... The expression of miR-129 has also been found to be altered in osteosarcoma. Certain studies detected the expression of HIF1A-AS2 and miR-129-5p in osteosarcoma cells, and used dual-luciferase reporter assays and other methods to determine the interaction between the two (24)(25)(26); the results showed that the increased expression of HIF1A-AS2 inhibited osteosarcoma cell proliferation and cancer cell invasion by altering miR-129-5p expression (5). LIM homeobox 2 (LHX2) is a protein-coding gene; its protein, consisting of two zinc finger domains, participates in cell differentiation and embryonic development (27,28). ...
An increasing number of studies indicate that microRNAs (miRNAs/miRs) are involved in diverse biological signaling pathways and play important roles in the progression of various diseases, including both oncological and non-oncological diseases. These small non-coding RNAs can block translation, resulting in a low expression level of target genes. miR-129 is an miRNA that has been the focus of considerable research in recent years. A growing body of evidence shows that the miR-129 family not only functions in cancer, including osteosarcoma, nasopharyngeal carcinoma, and ovarian, prostate, lung, breast and colon cancer, but also in non-cancerous diseases, including heart failure (HF), epilepsy, Alzheimer's disease (AD), obesity, diabetes and intervertebral disc degeneration (IVDD). It is therefore necessary to summarize current research progress on the role of miR-129 in different diseases. The present review includes an updated summary of the mechanisms of the miR-129 family in oncological and non-oncological diseases. To the best of our knowledge, this is the first review focusing on the role of miR-129 in non-cancerous diseases such as obesity, HF, epilepsy, diabetes, IVDD and AD.
... Some studies have reported the effect of lncRNA on osteosarcoma cells. LncRNA HIF1A-AS2 promotes the progression of osteosarcoma by regulating the function of miR-129-5p [12]. LncRNA KCNQ1OT1 functions as a competing endogenous RNA (ceRNA) for miR-4458, regulating the expression of CCND2 and enhancing the progression of osteosarcoma [13]. ...
Osteosarcoma is a malignant tumor with high mortality in children and adolescents. The mechanism of osteosarcoma metastasis is currently unclear. Abnormal expression of long non-coding RNA (lncRNA) plays an important role in tumor metastasis. We used bioinformatics to analyze the differences in gene expression between osteosarcoma in situ and osteosarcoma lung metastases. CCK-8 was used to detect the effect of lncRNA LOC100129620 on the proliferation of osteosarcoma cells. The effect of LOC100129620 on the invasion of osteosarcoma cells was assessed by Transwell assay. The regulatory effect of LOC100129620 on miR-335-3p was examined using RNA pull-down and luciferase reporter gene assays. The effect of LOC100129620 on the polarization of macrophages was detected by quantitative real-time fluorescent PCR. The results show that LOC100129620 can promote the proliferation and migration of osteosarcoma cells. LOC100129620 can promote the proliferation of osteosarcoma in vivo. LOC100129620 can bind to miR-335-3p and regulate its function. MiR-335-3p mediates the regulatory effects of LOC100129620 on CDK6. LOC100129620 promotes the formation of blood vessels and the polarization of macrophages. The LOC100129620/miR-335-3p/CDK6 signaling pathway promotes the metastasis of osteosarcoma by regulating the proliferation of osteosarcoma cells, angiogenesis, and macrophage polarization.
... [18][19][20] miRNAs bind complementary target mRNAs, resulting in mRNA translational inhibition and/or degradation. 21 miRNA dysregulation is detected in human OS, [22][23][24] associated with OS tumorigenesis, progression, and therapy resistance. 25,26 Here we identify a MAFG-targeting miRNA: microRNA-4660 (miR-4660). ...
... miRNA binds the 3 0 UTR of the complementary mRNAs, causing targeted mRNA translation inhibition and/or mRNA degradation. 25,26 miRNA is often dysregulation in human OS [22][23][24] and is associated with tumorigenesis progression. 25,26 The potential function of miR-4660 is largely unknown. ...
Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. MAFG forms a heterodimer with Nrf2 (NF-E2-related factor 2), binding to antioxidant response element (ARE) that is required for Nrf2 signaling activation. We found that MAFG mRNA and protein expression is significantly elevated in human OS tissues as well as in established and primary human OS cells. In human OS cells, MAGF silencing or knockout largely inhibited OS cell growth, proliferation and migration, simultaneously inducing oxidative injury and apoptosis activation. Conversely, ectopic overexpression of MAFG augmented OS cell progression in vitro. microRNA-4660 (miR-4660) directly binds the 3’-untranslated region (UTR) of MAFG mRNA in the cytoplasm of OS cells. MAFG 3’-UTR luciferase activity and expression as well as OS cell growth were largely inhibited with forced miR-4660 overexpression, but augmented with miR-4660 inhibition. In vivo, MAGF shRNA or forced overexpression of miR-4660 inhibited subcutaneous OS xenograft growth in severe combined immunodeficient mice. Furthermore, MAFG silencing or miR-4660 overexpression inhibited OS xenografts in situ growth in proximal tibia of the nude mice. In summary, MAFG overexpression-driven OS cell progression is inhibited by miR-4660. The miR-4660-MAFG axis could be novel therapeutic target for human OS.
... 11 HIF1A-AS2 expression is positively correlated with the development of osteosarcoma, bladder cancer, breast cancer and colorectal cancer. [12][13][14][15] The roles of HIF1A-AS2 in NSCLC have not been discovered. Our current study has shown that HIF1A-AS2 expression was upregulated in NSCLC tissues and its downregulation attenuated proliferation, migration and invasion while promoting apoptosis. ...
... 19 HIF1A-AS2 has been reported to participate in several cancers, such as osteosarcoma, bladder cancer, breast cancer and colorectal cancer. [12][13][14][15] Its function in NSCLC has yet to be described. Loss-of-function assays indicated that HIF1A-AS2 knockdown suppressed proliferation, migration and invasion while inducing apoptosis. ...
... 21 HIF1A-AS2 was also found to sponge several miRNAs, such as miR-129-5p, miR-548c-3p and miR-665. 12,22,23 In our study, we demonstrated that HIF1A-AS2 interacted with miR-153-5p. We showed that miR-153-5p expression was upregulated after HIF1A-AS2 knockdown, and HIF1A-AS2 level was negatively correlated with miR-153-5p expression in NSCLC tissues. ...
Background
Long noncoding RNA (lncRNA) plays a critical role in initiating lung cancer. This study aims to research the function and mechanism of lncRNA HIF1A-AS2 in regulating non-small cell lung cancer (NSCLC) progression.
Methods
qRT-PCR was used to analyze gene expression. The CCK-8 assay was performed to detect cell proliferation. The Transwell assay was conducted to examine cell migration and invasion. A Caspase3 activity detection kit was utilized to analyze apoptosis. The luciferase reporter assay was carried out to research interactions of HIF1A-AS2, miR-153-5p and S100A14.
Results
HIF1A-AS2 expression was raised in NSCLC tissues and cell lines. The HIF1A-AS2 level was increased in advanced NSCLC tumor tissues. High HIF1A-AS2 expression was related to poor prognosis. HIF1A-AS2 knockdown decreased proliferation, migration and invasion while promoting apoptosis. HIF1A-AS2 was the sponge for miR-153-5p, and miR-153-5p targeted S100A14. HIF1A-AS2 promoted S100A14 expression through regulating miR-153-5p.
Conclusion
The HIF1A-AS2/miR-153-5p/S100A14 axis plays a crucial role in promoting NSCLC progression.
