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Interference with circRNA DOCK1 inhibits hepatocellular carcinoma cell proliferation, invasion and migration by

Yujuan Lu1, Jingzhi Zhang2, Yanhui Wu3

  • 1Department of Infectious Diseases, Zibo Central Hospital, Zibo, Shandong 255036, P.R. China.

Molecular Medicine Reports
|June 29, 2021
PubMed

Insights

Circular RNA DOCK1 promotes hepatocellular carcinoma (HCC) progression by downregulating miR-654-5p and upregulating SMAD2. Inhibiting circRNA DOCK1 suppresses HCC cell proliferation, invasion, and migration.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death globally.
  • Circular RNAs (circRNAs) are increasingly recognized for their roles in various cancers, including HCC.
  • Understanding the specific functions of circRNAs like DOCK1 in HCC pathogenesis is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of circular RNA dedicator of cytokinesis 1 (circRNA DOCK1) in hepatocellular carcinoma (HCC).
  • To determine if circRNA DOCK1 influences HCC cell proliferation, invasion, and migration.
  • To elucidate the regulatory mechanism involving the microRNA (miR)-654-5p/SMAD2 axis.

Main Methods:

  • Reverse transcription-quantitative PCR (RT-qPCR) to measure expression levels of circRNA DOCK1, miR-654-5p, and SMAD2 mRNA.
  • Western blot analysis to assess SMAD2 protein expression.
  • Cell Counting Kit-8, clone formation, wound healing, and Transwell assays to evaluate cell viability, proliferation, migration, and invasion.
  • Dual-luciferase reporter assays to confirm interactions between circRNA DOCK1, miR-654-5p, and SMAD2.

Main Results:

  • Expression of circRNA DOCK1 and SMAD2 was elevated, while miR-654-5p was decreased in HCC cells.
  • circRNA DOCK1 directly targets miR-654-5p, and miR-654-5p directly targets SMAD2.
  • Interference with circRNA DOCK1 inhibited HCC cell proliferation, invasion, and migration by upregulating miR-654-5p.
  • Knockdown of circRNA DOCK1 effects were partially reversed by miR-654-5p inhibition and SMAD2 overexpression.

Conclusions:

  • circRNA DOCK1 plays a significant role in promoting HCC progression.
  • circRNA DOCK1 exerts its oncogenic effects by regulating the miR-654-5p/SMAD2 axis.
  • Targeting circRNA DOCK1 may represent a potential therapeutic strategy for HCC.
Keywords:
circular RNA dedicator of cytokinesis 1hepatocellular carcinomainvasion and migrationmicroRNA‑654-5p/SMAD2 axisproliferation

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