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Long non-coding RNA CTBP1-AS2 enhances cervical cancer progression via up-regulation of ZNF217 through sponging miR-3163.

ABSTRACT: Background:Long non-coding RNAs (lncRNAs) play significant roles in tumorigenesis and can contribute to identification of novel therapeutic targets for cancers. This paper was aimed at exploring the role of CTBP1 divergent transcript (CTBP1-AS2) in cervical cancer (CC) progression. Methods:qRT-PCR and western blot assays were used to detect relevant RNA and protein expressions. In vitro functional assays, including CCK8, EdU, TUNEL and transwell assays were applied to explore the functions of CTBP1-AS2 in CC cell proliferation, apoptosis and migration. In vivo animal study was utilized to investigate the role of CTBP1-AS2 in tumor growth. Luciferase reporter, RNA pull down and RIP assays were performed to determine the specific mechanical relationship between CTBP1-AS2, miR-3163 and ZNF217. Results:CTBP1-AS2 was significantly overexpressed in CC cell lines. Knockdown of CTBP1-AS2 curbed cell proliferation, migration and invasion, while stimulated cell apoptosis in vitro. CTBP1-AS2 facilitated xenograft tumor growth in vivo. Cytoplasmic CTBP1-AS2 was found to be a miR-3163 sponge in CC cells. MiR-3163 inhibition abolished the anti-tumor effects of CTBP1-AS2 knockdown. Additionally, Zinc finger protein 217 (ZNF217) was identified as a direct target of miR-3163. CTBP1-AS2 acted as a miR-3163 sponge to elevate ZNF217 expression. ZNF217 up-regulation abrogated the tumor suppressing effects of CTBP1-AS2 knockdown. Conclusion:CTBP1-AS2 regulates CC progression via sponging miR-3163 to up-regulate ZNF217.

SUBMITTER: Yang S

PROVIDER: S-EPMC7388209 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long non-coding RNA CTBP1-AS2 enhances cervical cancer progression via up-regulation of ZNF217 through sponging miR-3163.

Yang Shanshan S Shi Feng F Du Yuting Y Wang Zhao Z Feng Yue Y Song Jiayu J Liu Yunduo Y Xiao Min M

Cancer cell international 20200728

<h4>Background</h4>Long non-coding RNAs (lncRNAs) play significant roles in tumorigenesis and can contribute to identification of novel therapeutic targets for cancers. This paper was aimed at exploring the role of CTBP1 divergent transcript (CTBP1-AS2) in cervical cancer (CC) progression.<h4>Methods</h4>qRT-PCR and western blot assays were used to detect relevant RNA and protein expressions. In vitro functional assays, including CCK8, EdU, TUNEL and transwell assays were applied to explore the ...[more]

PMID: 32742190

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Project description:BackgroundHepatocellular carcinoma (HCC) is the major histological type of liver cancer with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNA) has been proved to be associated with various cancer types, while its regulation in HCC is largely unknown.MethodsTo figure out the specific role of lncRNA EPB41L4A-AS2 in HCC. Fluorescence in situ hybridization (FISH) was first used to determine the cellular sublocalization of EPB41L4A-AS2 to determine its primary mode of action. QRT-PCR, Western blot and hematoxylin-eosin staining were then used to measure the expression of genes in cells and tissues. Cell proliferation and invasion assays were performed to determine the effects of EPB41L4A-AS2, miR-301a-5p and FOXL1 on the malignant phenotype of tumor cells. With luciferase reporter assay, the direct interaction between target genes were further confirmed for research on molecular mechanism. Finally, the mice hepatocarcinoma model was also established to disclose the tumor suppressor effects of EPB41L4A-AS2 in vivo.ResultsHere, we have identified a novel lncRNA EPB41L4A-AS2, which is significantly downregulated both in HCC cells and tissues, and plays a negative regulatory role in HCC proliferation and invasion. Mechanistically, cytoplasmic lncRNA EPB41L4A-AS2 functions as an efficient miR-301a-5p sponge, thereby release the expression inhibition of forkhead box L1 (FOXL1). Indeed, lncRNA EPB41L4A-AS2 inhibits proliferation and migration by upregulating FOXL1 expression and FOXL1 was confirmed as a direct target of miR-301a-5p. MiR-301a-5p shows an inverse correlation with EPB41L4A-AS2 expression and was verified as a direct target of EPB41L4A-AS2 as well. Correspondingly, FOXL1 and miR-301a-5p show opposite biological effects in cell proliferation and migration. Moreover, miR-301a-5p overexpression rescued the EPB41L4A-AS2 upregulation induced depression in proliferation, migration and invasion of HCC cells, as well as promotion effect on FOXL1 expression. Also, in vivo experiments proved that EPB41L4A-AS2 suppress tumor growth and extrahepatic metastasis (lung) via the miR-301a-5p-FOXL1 axis.ConclusionsTaken together, this research revealed a concrete mechanism of lncRNA EPB41L4A-AS2 in HCC, which may serve as a potential biomarkers and novel therapeutic targets for further clinical application.

Dataset Information

Long non-coding RNA CTBP1-AS2 enhances cervical cancer progression via up-regulation of ZNF217 through sponging miR-3163.

Publications

Long non-coding RNA CTBP1-AS2 enhances cervical cancer progression via up-regulation of ZNF217 through sponging miR-3163.

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