LINC01798/miR-17-5p axis regulates ITGA8 and causes changes in tumor microenvironment and stemness in lung adenocarcinoma

Front Immunol. 2023 Feb 23:14:1096818. doi: 10.3389/fimmu.2023.1096818. eCollection 2023.

Abstract

Integrins are closely related to the occurrence and development of tumors. ITGA8 encodes the alpha 8 subunit of the heterodimeric integrin alpha8beta1. Studies on the role of this gene in the occurrence and development of lung cancer are scarce. The examination of public databases revealed that ITGA8 expression was significantly lower in tumor tissue than that in normal tissue, especially in lung cancer, renal carcinoma, and prostate cancer. Survival analysis of patients with lung adenocarcinoma revealed that higher ITGA8 expression had better prognosis. ITGA8 was positively related to immune checkpoints and immunomodulators, whereas B cell, CD4+ T cell, CD8+ T cell, neutrophil, macrophage, and dendritic cell infiltration had the same correlation. Moreover, ITGA8 was negatively related to cancer stemness. We used an online database to predict the miRNAs and lncRNAs that regulate ITGA8 and obtained the regulatory network of ITGA8 through correlation analysis and Kaplan-Meier survival analysis. Quantitative real-time PCR and western blot analyses showed that LINC01798 regulates ITGA8 expression through miR-17-5p. Therefore, the regulatory network of ITGA8 may serve as a new therapeutic target to improve the prognosis of patients with lung cancer.

Keywords: ITGA8; LUAD; TMB; cancer cell stemness; immune microenvironment; lncRNA; miRNA; regulatory network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell*
  • Humans
  • Integrin alpha Chains
  • Kidney Neoplasms*
  • Lung
  • Lung Neoplasms*
  • Male
  • MicroRNAs*
  • Prostatic Neoplasms
  • Tumor Microenvironment

Substances

  • Integrin alpha Chains
  • ITGA8 protein, human
  • MicroRNAs
  • MIRN17 microRNA, human

Grants and funding

This work was supported by the National Natural Science Foundation of China (82172569, 82072595 and 61973232), Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-061B), Tianjin Health Science and technology project (TJWJ2022XK005 and ZC20179).