Identification of a Novel circ_0010235/miR-1249-3p/HOXA13 Axis in Lung Adenocarcinoma

Biochem Genet. 2022 Oct;60(5):1657-1675. doi: 10.1007/s10528-021-10181-5. Epub 2022 Jan 25.

Abstract

Lung adenocarcinoma (LUAD) is an aggressive malignancy with a poor prognosis. In this study, we explored the critical role and mechanism of circ_0010235 in the pathogenesis of LUAD. The expression levels of circ_0010235, microRNA (miR)-1249-3p, and homeobox A13 (HOXA13) were gauged by quantitative real-time PCR (qRT-PCR) and Western blot. Cell proliferation, cycle progression, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-Deoxyuridine (Edu), flow cytometry, and transwell assays, respectively. The direct relationship between miR-1249-3p and circ_0010235 or HOXA13 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. Xenograft experiments were used to examine the role of circ_0010235 in vivo. Circ_0010235 was significantly overexpressed in human LUAD. Silencing of circ_0010235 hindered LUAD cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0010235 targeted and inhibited miR-1249-3p. Moreover, circ_0010235 depletion repressed cell malignant behaviors by upregulating miR-1249-3p. HOXA13 was identified as a direct and functional target of miR-1249-3p. Furthermore, circ_0010235 regulated HOXA13 expression by competing for shared miR-1249-3p. Our findings demonstrate that the circ_0010235/miR-1249-3p/HOXA13 axis is implicated in the pathogenesis of LUAD.

Keywords: HOXA13; Lung adenocarcinoma; Progression; circ_0010235; miR-1249-3p.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / metabolism
  • Adenocarcinoma of Lung* / pathology
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Homeodomain Proteins* / genetics
  • Humans
  • Lung Neoplasms* / pathology
  • MicroRNAs* / genetics
  • RNA, Circular* / genetics

Substances

  • Homeodomain Proteins
  • MIRN1249 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • homeobox protein HOXA13