A FUS-LATS1/2 Axis Inhibits Hepatocellular Carcinoma Progression via Activating Hippo Pathway

Le Bao1, Lei Yuan1, Pengfei Li1

  • 1Department of Intervention, Xuzhou Cancer Hospital, Xuzhou Hospital Affiliated to Jiangsu University, Xuzhou, China.

Abstract

Insights

Fused in sarcoma (FUS) protein suppresses hepatocellular carcinoma (HCC) progression by stabilizing LATS1/2, activating the Hippo pathway. FUS and LATS1/2 are downregulated in HCC tissues.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The role of the RNA-binding protein FUS (fused in sarcoma) in hepatocellular carcinoma (HCC) remains largely unknown.
  • Understanding FUS's function is crucial for developing new therapeutic strategies against HCC.

Purpose of the Study:

  • To investigate the role and underlying mechanisms of FUS in HCC progression.
  • To explore the relationship between FUS, LATS1/2, and the Hippo pathway in HCC.

Main Methods:

  • Utilized quantitative reverse transcription PCR (qRT-PCR), western blot, cell viability, migration, invasion, and tumor sphere formation assays.
  • Conducted transcriptome analysis via RNA-sequencing, luciferase reporter assays, and RNA immunoprecipitation (RIP) assays.
  • Analyzed FUS and LATS1/2 expression levels in HCC and adjacent normal tissues.

Main Results:

  • Overexpression of FUS inhibited HCC cell viability, migration, invasion, and stemness.
  • FUS was found to interact with and stabilize LATS1/2, promoting its expression and activating the Hippo pathway.
  • FUS and LATS1/2 levels were positively correlated and significantly downregulated in HCC tissues.

Conclusions:

  • The FUS/LATS1/2 axis plays a critical role in inhibiting HCC progression.
  • Activation of the Hippo pathway by FUS/LATS1/2 represents a potential therapeutic target for HCC.

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