C1orf74 positively regulates the EGFR/AKT/mTORC1 signaling in lung adenocarcinoma cells

PeerJ. 2022 Aug 22:10:e13908. doi: 10.7717/peerj.13908. eCollection 2022.

Abstract

Background: Lung adenocarcinoma (LUAD) is a major type of lung cancer with poor prognosis and low 5-year survival rate, which urgently needs further investigation in order to elucidate its mechanisms completely and discover novel therapeutic targets. C1orf74 is a novel protein with unknown function either in normal cells or cancer cells. The aim of this study is to investigate the expression and function of C1orf74 in LUAD cells.

Methods: The expression of C1orf74 in LUAD was analyzed using the LUAD datasets from public databases. The prognostic value of C1orf74 in LUAD was analyzed using Kaplan-Meier Plotter. C1orf74 expression in LUAD cell line A549, H1993 and HCC827 was silenced using small interfering RNA, and then the effects of C1orf74 knockdown on proliferation, migration and invasion of LUAD cells were detected by colony formation assay and Transwell assay, the role of C1orf74 in EGFR/AKT/mTORC1 signaling pathway was examined by Western blot, and the function of C1orf74 in cell cycle was detected by flow cytometry.

Results: The results of LUAD clinical data showed that C1orf74 was upregulated in LUAD tissues, and its high expression was associated with poor prognosis. The results from cultured LUAD cells demonstrated that C1orf74 knockdown inhibited cell proliferation, migration and invasion, but induced cell cycle arrest and autophagy. Moreover, C1orf74 knockdown suppressed EGFR/AKT/mTORC1 signaling in LUAD cells. In conclusion, the present study revealed that C1orf74 is upregulated in LUAD tissues and plays an oncogenic role in LUAD, and that C1orf74 positively regulates cell proliferation and mobility through the EGFR/AKT/mTORC1 signaling pathway in LUAD cells.

Keywords: A549; C1orf74; EGFR/AKT/mTORC1 signaling; H1993; HCC827; Lung adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • Mechanistic Target of Rapamycin Complex 1 / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Signal Transduction / genetics

Substances

  • Proto-Oncogene Proteins c-akt
  • Mechanistic Target of Rapamycin Complex 1
  • ErbB Receptors
  • EGFR protein, human

Grants and funding

The present study was supported by the National Natural Science Foundation of China (No. 32160156), the National Natural Science Foundation of Guangxi (No. 2020GXNSFAA297209), the Special Fund of the Central Government Guiding Local Scientific and Technological Development by Guangxi Science and Technology Department (ZY21195024), the Science and Technology Planned Project in Guilin (20210102-1), the Guangxi Distinguished Experts Special Fund (2019B12), and the Research Enhancement Project for Junior Faculty in Higher Education Institutes of Guangxi (Grant No. 2022KY0480). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.