Investigation the Role of Autophagy in Non-Small Cell Lung Cancer

Asian Pac J Cancer Prev. 2021 Mar 1;22(3):947-955. doi: 10.31557/APJCP.2021.22.3.947.

Abstract

Objective: Recent studies have shown the role of autophagy in different types of cancer including lung cancer. MicroRNAs are considered as key factors in regulation of autophagy related genes. miR-30d, miR-204-5p and miR-20a are regulatory markers which can suppress the expression of beclin1, LC3, bcl2 and ULK1 as their target genes and they lead to decrement of autophagy in human cancer cells. Moreover, epigenetic modifications DNA methylation has been indicated in regulation of autophagy in different stages of cancer.

Methods: In this study, the expression levels of miR-30d, miR-204-5p and miR-20a as well as their target genes were analyzed in 30 non-small cell lung cancers (NSCLCs) patients sample and adjacent normal tissues by real-time qPCR. In addition, DNA methylation of beclin1, LC3, bcl2 and ULK1 genes were assessed by MS-HRM method.

Results: MiR-30d (p value= 0.01) and miR-204-5p (P=0.048) significantly down-regulated in tumor samples compared to normal adjacent tissues, while there was no significant change in expression level of miR-20a. On the other hand, target genes expression level was significantly increased in NSCLC tissues, however methylation pattern of the target gene promoters, did not show any significant alteration.

Conclusion: These results indicate roles for miR-30d, miR-204-5p as tumor suppressor genes as well as target genes as oncogenes in NSCLC patients. Although these factors may have a significant role in NSCLC progression, further studies are necessary to investigate the implications of these findings for treatment of lung cancer. <br />.

Keywords: Autophagy; DNA Methylation; MicroRNAs; non-small cell lung cancer.

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / pathology
  • Autophagy / genetics*
  • Autophagy-Related Protein-1 Homolog / genetics
  • Beclin-1 / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • DNA Methylation
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / genetics

Substances

  • BCL2 protein, human
  • BECN1 protein, human
  • Beclin-1
  • Intracellular Signaling Peptides and Proteins
  • MAP1LC3A protein, human
  • MIRN204 microRNA, human
  • MIRN20a microRNA, human
  • MIRN30d microRNA, human
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Autophagy-Related Protein-1 Homolog
  • ULK1 protein, human