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Long non-coding RNA OIP5-AS1 promotes the progression of esophageal cancer by regulating miR-30a/VOPP1 expression.

ABSTRACT: Long non-coding RNAs (lncRNAs) serve an important role in the development of esophageal cancer (EC), which is the eighth most common type of cancer worldwide. lncRNA opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) is associated with human malignancy. However, the biological roles of OIP5-AS1 in the development of EC remain unclear. In the present study, transfection was conducted, and reverse transcription-quantitative PCR and western blot analysis were used for the detection of mRNA and protein expression, respectively. Furthermore, dual-luciferase reporter and RNA immunoprecipitation assays were used to study the interaction between miRNA and lncRNA or genes. The results revealed that OIP5-AS1 expression in EC tissues and cultured EC cells was upregulated, microRNA-30a (miR-30a) expression was downregulated. OIP5-AS1-knockdown suppressed the proliferation, migration and invasion of EC9706 and EC109 cells. miR-30a was confirmed to interact with OIP5-AS1, and miR-30a-mimics transfection ameliorated the effects of OIP5-AS1 in EC cells. Vesicular overexpressed in cancer prosurvival protein 1 (VOPP1) was verified as the direct target of miR-30a. VOPP1 expression was positively correlated with OIP5-AS1 expression in EC cells. Overexpression of VOPP1 ameliorated the negative effects of OIP5-AS1-knockdown on EC9706 and EC109 cells. In conclusion, OIP5-AS1 promoted the proliferation, migration and invasion of EC cells by increasing VOPP1 expression by sponging miR-30a.

SUBMITTER: Xu J

PROVIDER: S-EPMC8299025 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPapillary thyroid cancer (PTC) is the most common type of cancer of the endocrine system. Long noncoding RNAs (lncRNAs) are emerging as a novel class of gene expression regulators associated with tumorigenesis. Through preexisting databases available for differentially expressed lncRNAs in PTC, we uncovered that lncRNA OIP5-AS1 was significantly upregulated in PTC tissues. However, the function and the underlying mechanism of OIP5-AS1 in PTC are poorly understood.MethodsExpression of lncRNA OIP5-AS1 and miR-98 in PTC tissue and cells were measured by quantitative real-time PCR (qRT-PCR). And expression of METTL14 and ADAMTS8 in PTC tissue and cells were measured by qRT-PCR and western blot. The biological functions of METTL14, OIP5-AS1, and ADAMTS8 were examined using MTT, colony formation, transwell, and wound healing assays in PTC cells. The relationship between METTL14 and OIP5-AS1 were evaluated using RNA immunoprecipitation (RIP) and RNA pull down assay. And the relationship between miR-98 and ADAMTS8 were examined by luciferase reporter assay. For in vivo experiments, a xenograft model was used to investigate the effects of OIP5-AS1 and ADAMTS8 in PTC.ResultsFunctional validation revealed that OIP5-AS1 overexpression promotes PTC cell proliferation, migration/invasion in vitro and in vivo, while OIP5-AS1 knockdown shows an opposite effect. Mechanistically, OIP5-AS1 acts as a target of miR-98, which activates ADAMTS8. OIP5-AS1 promotes PTC cell progression through miR-98/ADAMTS8 and EGFR, MEK/ERK pathways. Furthermore, RIP and RNA pull down assays identified OIP5-AS1 as the downstream target of METTL14. Overexpression of METTL14 suppresses PTC cell proliferation and migration/invasion through inhibiting OIP5-AS1 expression and regulating EGFR, MEK/ERK pathways.ConclusionsCollectively, our findings demonstrate that OIP5-AS1 is a METTL14-regulated lncRNA that plays an important role in PTC progression and offers new insights into the regulatory mechanisms underlying PTC development.

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Long non-coding RNA OIP5-AS1 promotes the progression of esophageal cancer by regulating miR-30a/VOPP1 expression.

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