Dataset Information

Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression.

ABSTRACT: Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown. In this study, we identified a novel upregulated circRNA, hsa_circ_0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored the biological role of hsa_circ_0000326 using gain- and loss-of-function assays in adenocarcinoma cells. Bioinformatics databases were used to screen for potential target miRNAs and the luciferase reporter assays and RNA-FISH further validated the interaction. Downstream protein was detected by western blot. Finally, we established xenografts in nude mice to assess the function of hsa_circ_0000326 in vivo. We found that high expression of hsa_circ_0000326 was correlated with tumor size, regional lymph node status and differentiation in human lung adenocarcinoma. Additionally, we conducted gain- and loss-of-function assays and found that hsa_circ_0000326 acted as a positive regulator of cell proliferation and migration and a negative regulator of apoptosis. Mechanistic studies showed that hsa_circ_0000326 acted as a miR-338-3p sponge and altered the function of miR-338-3p, which in turn upregulated the expression of the downstream target RAB14 and affected the proliferation, migration and apoptosis of lung adenocarcinoma cells. Collectively, our study results reveal crucial roles for hsa_circ_0000326 in the proliferation, migration and apoptosis of lung adenocarcinoma cells and suggest that hsa_circ_0000326 may represent a potential therapeutic target in patients with lung adenocarcinoma.

SUBMITTER: Xu Y

PROVIDER: S-EPMC7132982 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression.

Xu Yuzhu Y Yu Jun J Huang Zhenli Z Fu Bohua B Tao Yu Y Qi Xuefei X Mou Yong Y Hu Yinan Y Wang Yi Y Cao Yong Y Jiang Dingsheng D Xie Jungang J Xu Yongjian Y Zhao Jianping J Xiong Weining W

Journal of experimental & clinical cancer research : CR 20200405 1

<h4>Background</h4>Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown.<h4>Methods</h4>In this study, we identified a novel upregulated circRNA, hsa_circ_0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored t ...[more]

PMID: 32248836

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Project description:BackgroundLung cancer refers to the occurrence of malignant tumors in the lung, and squamous cell carcinoma is one of the most common pathological types of non-small cell lung cancer. Studies have shown that microRNAs (miRNAs) play an important role in the occurrence, development, early diagnosis, and treatment of lung cancer. This study aimed to explore the role and possible mechanism of MicroRNA-338-3p (miR-338-3p) in lung squamous cell carcinoma (LUSC).MethodIn this study, we compared 238 LUSC patients with relatively high miR-338-3p expression levels with 238 miR-338-3p expression levels in The Cancer Genome Atlas (TCGA)-LUSC dataset using first-line gene set enrichment analysis (GSEA). Second, the mRNA expression of miR-338-3p, FGFR2, and fibroblast growth factor receptor substrate 2 (FRS2) in 30 lung cancers and adjacent lung tissues was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Finally, in vitro experiments were conducted, whereby the expression levels of miR-338-3p in lung cancer cells (H1703, SKMES1, H2170, H520) and normal lung epithelial cells (16HBE) were detected using qRT-PCR. miR-338-3p was overexpressed in lung cancer cells (H1703), and the cell proliferation (cell counting kit-8 [CCK8] assay), colony formation, cell apoptosis, cell cycle (BD-FACSVerse assay, Becton Dickinson, Bedford, MA, USA), cell invasion, and migration (Transwell assay, Thermo Fischer Corporation, Waltham, MA, USA) were detected.ResultsWe found that the expression of miR-338-3p was significantly reduced in LUSC tissues (p < 0.001) and cancer cell lines (P < 0.01), and miR-338-3p was significantly negatively correlated with the expression of FGFR2 (P < 0.001) and FRS2 (P < 0.01). Furthermore, overexpression of miR-338-3p inhibited proliferation (P < 0.001), migration, and invasion (P < 0.001) of LUSC cell lines and increased apoptosis in the G1 phase (P < 0.001) and cell cycle arrest (P < 0.05).ConclusionsOur study demonstrates that miR-338-3p inhibits tumor cell proliferation and migration by targeting FGFR2 and FRS2 in LUSC. We believe that miR-338-3p may be a promising target for the treatment of LUSC.

Dataset Information

Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression.

Publications

Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression.

Similar Datasets

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