miR-3613-5p enhances the metastasis of pancreatic cancer by targeting CDK6

Cell Cycle. 2020 Nov;19(22):3086-3095. doi: 10.1080/15384101.2020.1831254. Epub 2020 Oct 19.

Abstract

Pancreatic cancer (PC) is a leading cause of cancer mortality and is expected to continue increasing incidence. Abnormally expressed microRNAs have been demonstrated tightly correlated with the development and progression of PC. However, the molecular mechanisms remain largely unknown. In this study through combing both the TCGA database and our two verification PC cohorts, we found the consistent reduction of miR-3613-5p in PC tumors, which significantly correlated with reduced cumulative survival rate among PC patients. PC patients with higher lymph node metastasis rate show reduced miR-3613-5p expression. Through further mechanistic investigation, we demonstrate that miR-3613-5p down-regulated CDK6 in repressing the metastasis capacity of PC cells in vitro and in vivo. Elevated CDK6 were also found in PC samples, which also correlate with poor prognosis. Thus, our study found a novel tumor repressor miR-3613-5p in PC progression.

Keywords: CDK6; Pancreatic cancer; metastasis; miR-3613-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase 6 / genetics
  • Cyclin-Dependent Kinase 6 / metabolism*
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis / genetics*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Transplantation / methods
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Signal Transduction / genetics*
  • Survival Rate
  • Transfection

Substances

  • MIRN3613 microRNA, human
  • MicroRNAs
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6

Grants and funding

This work was supported by the National Natural Science Foundation of China (81803014, 81802424, 81802937, 81600406, and 81602043).