Down-regulation of circPTTG1IP induces hepatocellular carcinoma development via miR-16-5p/RNF125/JAK1 axis

Rui Peng1, Jun Cao1, Bing-Bing Su1

  • 1Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225009, Jiangsu, China.

Cancer Letters
|June 16, 2022
PubMed

Insights

Circular RNA circPTTG1IP suppresses hepatocellular carcinoma (HCC) by regulating the miR-16-5p/RNF125/JAK1 pathway. Low circPTTG1IP levels promote HCC, and JAK1 inhibitor filgotinib may benefit patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) play roles in hepatocellular carcinoma (HCC) progression.
  • Down syndrome individuals exhibit reduced solid tumor risk due to tumor suppressor genes on human chromosome 21 (HSA21).

Purpose of the Study:

  • To investigate the role of HSA21-derived circRNAs in HCC progression.
  • To identify specific circRNAs involved in HCC development and their underlying mechanisms.

Main Methods:

  • CircRNA-sequencing on HCC and peritumor tissues.
  • Quantitative reverse transcription PCR (qRT-PCR) for expression analysis.
  • In vitro and in vivo functional assays, luciferase reporter assays, RNA immunoprecipitation, and fluorescence in situ hybridization (FISH).

Main Results:

  • Circ_0061984 (circPTTG1IP) expression was significantly decreased in HCC tissues and associated with poor prognosis.
  • Elevated circPTTG1IP inhibited HCC progression in vitro and in vivo.
  • circPTTG1IP acts as a competing endogenous RNA (ceRNA) by sponging miR-16-5p, leading to increased RNF125 and subsequent degradation of JAK1 protein.

Conclusions:

  • circPTTG1IP functions as a tumor suppressor in HCC.
  • The circPTTG1IP/miR-16-5p/RNF125/JAK1 axis is a key pathway in HCC development.
  • Filgotinib, a JAK1 inhibitor, can restrict HCC progression in cases of low circPTTG1IP expression, suggesting potential therapeutic benefits.

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