nc-RNA-mediated high expression of CDK6 correlates with poor prognosis and immune infiltration in pancreatic cancer

Cancer Med. 2023 Feb;12(4):5110-5123. doi: 10.1002/cam4.5260. Epub 2022 Dec 1.

Abstract

Background: Emerging evidence manifests that cyclin-dependent kinase 6 (CDK6) plays an essential part in the initiation and progression of several types of human cancer, and its descending expression is correlated with an adverse prognosis. However, the precise role of CDK6 in Pancreatic cancer (PC) remains obscure.

Aims: To identify the potential ceRNA regulatory axis of CDK6 in PC and explore its relationship with immune cells and immune checkpoints.

Materials & methods: Using The Cancer Genome Atlas TCGA and GTEx data analyze the expression and survival of CDK6 in patients in pan-cancer, and cellular experiments were performed to verify the effect of CDK6 on cell function. Using GEPIA and STARBASE databases to analyze prognosis, expression and survival, and identify non coding RNA (ncRNA) that mediates CDK6 overexpression. The TIMER 2.0 database was used for immune correlation analysis.

Results: We revealed CDK6 might be an oncogene in PC, and the HOXA11-AS /NR2F1-AS1- miR-454-3p axis was identified as the possible upstream ncRNA-associated pathway of CDK6 in PC. In addition, CDK6 show significant association with three immune checkpoints (PD-L1, PD-L2, and HAVCR2), the infiltration level of immune cells, and immunity biomarkers.

Discussion: We discussed some applications of CDK6 in breast cancer, melanoma, and hemorrhagic malignancies. The role of miR-15a-5p, HOXA11-AS and NR2F1-AS1 in tumor development was also discussed based on existing studies. The potential mechanism of CDK6 affecting immune cells in pancreatic cancer was discussed.

Conclusions: Overall, these results established that nc-RNA-mediated high expression of CDK6 is associated with patient outcomes and immune invasion in pancreatic cancer.

Keywords: CDK6; HOXA11-AS; NR2F1-AS1; pancreatic cancer; tumor immune infiltration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase 6 / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology
  • Prognosis
  • RNA, Long Noncoding* / genetics

Substances

  • MicroRNAs
  • Cyclin-Dependent Kinase 6
  • RNA, Long Noncoding
  • CDK6 protein, human