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CircWDR37 promotes hepatocellular carcinoma tumorigenesis by mediating the miR-646/TRAF4 regulatory pathway

Jie Zhou1, Zhu Zhu2, Xi Zhang3

  • 1The Second Clinical College, The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang 550003, China.

Pathology, Research and Practice
|October 20, 2024
PubMed

Insights

Circular RNA hsa_circ_0004277 (circWDR37) promotes hepatocellular carcinoma (HCC) by sponging miR-646, leading to increased TRAF4. This circWDR37-miR-646-TRAF4 axis offers a potential therapeutic target for HCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Circular RNAs (CircRNAs) play a role in human cancers, including hepatocellular carcinoma (HCC).
  • Hsa_circ_0004277 (circWDR37) is upregulated in HCC, but its function in HCC progression is unclear.

Purpose of the Study:

  • To investigate the role and mechanism of circWDR37 in hepatocellular carcinoma (HCC) progression.
  • To elucidate the regulatory axis involving circWDR37, miR-646, and TRAF4 in HCC.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and western blot to assess expression levels.
  • Cellular assays (CCK-8, EdU, colony formation, flow cytometry, transwell, tube formation) to evaluate malignant phenotypes.
  • Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays to confirm molecular interactions.
  • In vivo xenograft mouse model to assess tumor growth.

Main Results:

  • CircWDR37 and TRAF4 were upregulated, while miR-646 was downregulated in HCC tissues and cells.
  • Silencing circWDR37 inhibited HCC cell proliferation, migration, invasion, and angiogenesis, and promoted apoptosis.
  • CircWDR37 directly targets miR-646, suppressing its expression and upregulating TRAF4.
  • Knockdown of circWDR37 suppressed HCC tumor growth in vivo.

Conclusions:

  • CircWDR37 acts as an oncogene in HCC by sponging miR-646, thereby upregulating TRAF4.
  • A novel regulatory axis, 'circWDR37-miR-646-TRAF4', is identified in HCC.
  • This axis represents a potential therapeutic target for hepatocellular carcinoma treatment.
Abstract

Keywords:
CircWDR37HCCMiR-646TRAF4

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