Effects of LncRNA MEG3 on immunity and autophagy of non-small cell lung carcinoma through IDO signaling pathway

World J Surg Oncol. 2021 Aug 16;19(1):244. doi: 10.1186/s12957-021-02346-8.

Abstract

Background: The study was done to investigate the effect of LncRNA MEG3 on the immunity and autophagy of non-small cell lung carcinoma through the IDO signaling pathway.

Methods: A total of 78 cases of early NSCLC patients (research group; RG) and 69 cases of health controls (control group; CG) during the same time were included. The contents of LncRNA MEG3 and miR-543 in peripheral blood and tissues and their diagnostic values for NSCLC were detected. The relationship between LncRNA MEG3 and miR-543 and their posttreatment contents and influence on the prognosis of NSCLC patients were tested. The expression of LncRNA MEG3, miR-543, and IDO (IDO1, IDO2, and TDO proteins) in the lung tissue of rats and the immune function in the CG and the RG were detected. The effects of LncRNA MEG3 and miR-543 on the biological behavior of NSCLC cells were determined. The role of LncRNA MEG3, miR-543, and IDO in NSCLC was verified.

Results: LncRNA MEG3 was low in peripheral blood and tissues, while miR-543 was high (P < 0.05); both had good diagnostic values for NSCLC (P < 0.05). LncRNA MEG3 had a negative correlation with miR-543 (P < 0.05) and influenced the prognosis of NSCLC patients (P < 0.05). LncRNA MEG3 in the lung tissue of rats using IDO inhibitor was elevated compared with that of lung carcinoma model rats (P < 0.05). The level of miR-543 was declined compared with that of lung carcinoma model rats (P < 0.05). The levels of IDO1, IDO2, and TDO proteins were evidently declined compared with those of lung carcinoma model rats (P < 0.05). Compared with lung carcinoma model rats, CD3+, CD4+, and CD4+/CD8+ of IDO inhibitor rats were elevated, while CD8+ was declined (P < 0.05). Cell proliferation and invasion ability and IDO1, IDO2, TDO, Beclin-1, and LC3-II proteins were declined in the sh-LncRNA MEG3 group (P < 0.05), while those in the mimics-miR-543 group were evidently elevated (P < 0.05). However, the double luciferase activity detection and RIP experiment confirmed that there was targeted regulation among them (P < 0.05).

Conclusion: MEG3 has low expression in NSCLC and affects the immunity and autophagy of NSCLC cells via regulating the miR-543/IDO signaling pathway, which is effective for the treatment of NSCLC.

Keywords: Autophagy; IDO signaling pathway; Immunity; LncRNA MEG3; Non-small cell lung carcinoma.

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics
  • Prognosis
  • RNA, Long Noncoding* / genetics
  • Rats
  • Signal Transduction

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • MEG3 non-coding RNA, human
  • MEG3 non-coding RNA, rat
  • MIRN543 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding