Circular RNA circ_0003028 contributes to tumorigenesis by regulating GOT2 via miR-1298-5p in non-small cell lung cancer

Bioengineered. 2021 Dec;12(1):2326-2340. doi: 10.1080/21655979.2021.1935064.

Abstract

Non-small cell lung cancer (NSCLC) is a common malignant tumor, with high morbidity and mortality. Circular RNA (circRNA) circ_0003028 was reported to be upregulated in NSCLC. This study is designed to explore the role and mechanism of circ_0003028 on NSCLC progression. In this work, circ_0003028, microRNA-1298-5p (miR-1298-5p), and glutamic oxaloacetic transaminase 2 (GOT2) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The localization of circ_0003028 was analyzed by subcellular fractionation assay. Cell proliferation, colony number, cell cycle progression, apoptosis, migration, invasion, and angiogenesis were measured by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, transwell, and tube formation assays. Protein levels of Beclin1, light chain 3 (LC3)-II/LC3-I, GOT2, proliferating cell nuclear antigen (PCNA) were examined by western blot assay. The binding relationship between miR-1298-5p and circ_0003028 or GOT2 was predicted by circular RNA Interactome or starbase and then verified by dual-luciferase reporter, RNA Immunoprecipitation (RIP), and RNA pull-down assays. The biological role of circ_0003028 on NSCLC tumor growth was examined by the xenograft tumor model in vivo. We reported that circ_0003028 and GOT2 were upregulated, and miR-1298-5p was decreased in NSCLC tissues and cells. Moreover, circ_0003028 knockdown curbed cell proliferative ability, migration, invasion, angiogenesis, and facilitate apoptosis and autophagy in NSCLC cells in vitro. Mechanical analysis discovered that circ_0003028 regulated GOT2 expression by sponging miR-1298-5p. Circ_0003028 silencing hindered the cell growth of NSCLC in vivo. Taken together, circ_0003028 knockdown could suppress NSCLC progression partly by regulating the miR-1298-5p/GOT2 axis, providing an underlying therapeutic target for NSCLC.

Keywords: Circ_0003028; GOT2; miR-1298-5p; non-small cell lung cancer.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Aspartate Aminotransferases* / genetics
  • Aspartate Aminotransferases* / metabolism
  • Carcinogenesis / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism

Substances

  • MIRN1298 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Aspartate Aminotransferases

Grants and funding

The authors have no funding to report.