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TANGO1 interacts with NRTN to promote hepatocellular carcinoma progression by regulating the PI3K/AKT/mTOR signaling

Jing Man1, Wanbiao Zhou1, Shi Zuo1

  • 1Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, Peoples Republic of China; Department of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, Peoples Republic of China.

Biochemical Pharmacology
|May 21, 2023
PubMed

Insights

Transport and Golgi organization 1 (TANGO1) promotes hepatocellular carcinoma (HCC) by enhancing proliferation and inhibiting apoptosis. TANGO1 interacts with neurturin (NRTN) to activate the PI3K/AKT/mTOR pathway, suggesting a new therapeutic target for HCC.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Transport and Golgi organization 1 (TANGO1), also known as MIA3, is part of the melanoma inhibitory activity (MIA) gene family.
  • The specific role of TANGO1 in hepatocellular carcinoma (HCC) pathogenesis remains largely unelucidated.

Purpose of the Study:

  • To investigate the role and underlying molecular mechanisms of TANGO1 in hepatocellular carcinoma (HCC) progression.
  • To explore the potential of the TANGO1/neurturin (NRTN) axis as a therapeutic target in HCC.

Main Methods:

  • RNA sequencing (RNA-seq) was employed to identify molecular pathways associated with TANGO1's function in HCC.
  • Endogenous co-immunoprecipitation (Co-IP) and confocal microscopy were used to confirm the interaction between TANGO1 and NRTN.
  • Functional assays assessed the impact of TANGO1 on HCC cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT).

Main Results:

  • TANGO1 was confirmed to promote HCC progression, characterized by increased proliferation, inhibited apoptosis, and enhanced EMT.
  • TANGO1 inhibition reversed these pro-tumorigenic effects in HCC cells.
  • TANGO1 was found to interact with neurturin (NRTN), and both proteins were shown to promote HCC progression via activation of the PI3K/AKT/mTOR signaling pathway.

Conclusions:

  • TANGO1 acts as an oncogene in hepatocellular carcinoma (HCC).
  • The TANGO1/NRTN axis promotes HCC by activating the PI3K/AKT/mTOR signaling pathway.
  • Targeting the TANGO1/NRTN axis presents a promising therapeutic strategy for HCC treatment.
Keywords:
Hepatocellular carcinomaMIA3NRTNPI3K/AKT/mTOR signaling pathwayTANGO1

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