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Alternative splicing-related long noncoding RNA ANRIL facilitates hepatocellular carcinoma by targeting the

Yifan Zhang1, Yiquan Lu1, Nan Wang1

  • 1Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Molecular Carcinogenesis
|February 27, 2024
PubMed

Insights

Long noncoding RNA ANRIL promotes hepatocellular carcinoma (HCC) progression by regulating alternative splicing. Depleting ANRIL impairs HCC cell growth and metastasis by modulating the miR-199a-5p/SRSF1 axis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Aberrant alternative splicing (AS) is a hallmark of hepatocellular carcinoma (HCC).
  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer, but their involvement in HCC's AS remains underexplored.
  • Our prior work implicated ANRIL in HCC-related AS.

Purpose of the Study:

  • To elucidate the precise role and underlying mechanism of ANRIL in HCC progression.
  • To investigate the relationship between ANRIL, microRNAs, and splicing factors in HCC.

Main Methods:

  • Validated ANRIL expression via real-time quantitative polymerase chain reaction.
  • Assessed protein levels of SRSF1 and Anillin using western blot and immunohistochemistry.
  • Conducted loss-of- and gain-of-function experiments in HCC cells.
  • Utilized dual-luciferase reporter assays to confirm interactions within the ANRIL/miR-199a-5p/SRSF1 pathway.

Main Results:

  • ANRIL was significantly upregulated in HCC, correlating with adverse clinicopathological features.
  • ANRIL depletion inhibited HCC cell proliferation, migration, tumorigenesis, and metastasis.
  • ANRIL functions as a molecular sponge for miR-199a-5p, leading to increased SRSF1 levels.
  • The ANRIL/miR-199a-5p/SRSF1 axis influences Anillin, a known HCC promoter.

Conclusions:

  • ANRIL is an alternative splicing-associated lncRNA that promotes HCC.
  • ANRIL drives HCC progression by modulating the miR-199a-5p/SRSF1 axis, with Anillin acting as a key downstream effector.
Keywords:
ANRILAnillinalternative splicinghepatocellular carcinomamiR‐199a‐5p/SRSF1 axis

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