miR-199a-3p plays an anti-tumorigenic role in lung adenocarcinoma by suppressing anterior gradient 2

Bioengineered. 2021 Dec;12(1):7859-7871. doi: 10.1080/21655979.2021.1967009.

Abstract

Previous studies have explored the association between protein-coding genes and microRNAs (miRNAs) in lung adenocarcinoma (LUAD). However, the influence of the miR-199a-3p/anterior gradient 2 (AGR2) axis in LUAD has not yet been fully explored. Therefore, this study aimed to examine the underlying roles of AGR2 and miR-199a-3p in the development of LUAD. The expression levels of miR-199a-3p and AGR2 in LUAD tissues and cells were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A luciferase assay was also performed to identify the interaction between AGR2 and miR-199a-3p. Moreover, the cell counting kit 8 (CCK-8), 5'-bromo-2'-deoxyuridine (BrdU), and adhesion assays were used along with flow cytometry to verify the malignancy of LUAD in vitro, while a xenograft tumor assay was performed to confirm the tumor growth in vitro. The findings showed a decrease in the expression of miR-199a-3p in LUAD. Additionally, miR-199a-3p overexpression inhibited the growth of LUAD cells in vitro and in vivo, while elevating the apoptosis rate of the cells. AGR2 knockdown had the same effect in the cells as that of miR-199a-3p overexpression. It was also found that miR-199a-3p directly targeted AGR2 in LUAD cells to suppress tumorigenesis. In conclusion, this study suggests that miR-199a-3p plays an anti-tumorigenic role in LUAD by targeting AGR2. Moreover, our study provides insights into the development of novel therapeutic targets for the treatment of LUAD.

Keywords: AGR2; MIR-199A-3P; cancer; lung adenocarcinoma; lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / metabolism
  • Adenocarcinoma of Lung* / pathology
  • Animals
  • Antineoplastic Agents / metabolism*
  • Cell Line, Tumor
  • Humans
  • Lung / pathology
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mucoproteins / genetics
  • Mucoproteins / metabolism*
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*

Substances

  • AGR2 protein, human
  • Antineoplastic Agents
  • MicroRNAs
  • Mucoproteins
  • Oncogene Proteins
  • mirn199 microRNA, human

Grants and funding

This work was supported by Science and Technology Project of Henan province (Grant No. 192102310374; recipient: Yi Wang) and Doctoral Research Initiation Fund of Affiliated Cancer Hospital of Zhengzhou University (Grant No. 3101030102; recipient: He Zhang).