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IFN-γ affects pancreatic cancer properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway

X-Y Shi1, X-L Zhang1, Q-Y Shi1

  • 1Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|January 17, 2022
PubMed
Abstract

Insights

Interferon gamma (IFN-γ) inhibits pancreatic cancer (PC) progression by downregulating MACC1 expression via the MACC1-AS1/MACC1 axis and AKT/mTOR pathway. This finding offers new therapeutic targets for PC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Metastasis-related in colon cancer 1 (MACC1) is implicated in various solid tumors.
  • The role of MACC1 in pancreatic cancer (PC) and the influence of Interferon gamma (IFN-γ) on its expression were previously unknown.
  • Investigating the mechanism of IFN-γ intervention on MACC1 expression in PC was the focus.

Purpose of the Study:

  • To elucidate the role of MACC1 in pancreatic cancer.
  • To investigate the mechanism by which IFN-γ affects MACC1 expression and pancreatic cancer cell behavior.
  • To explore the potential of the MACC1-AS1/MACC1 axis and AKT/mTOR pathway as therapeutic targets.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and western blot (WB) were used to assess MACC1 and MACC1-AS1 expression.
  • Cellular proliferation, migration, and invasion were evaluated using CCK8, EDU, colony formation, Transwell, and wound-healing assays.
  • The AKT/mTOR pathway was analyzed, and siRNA and lentiviral vectors were employed for gene manipulation.

Main Results:

  • IFN-γ significantly inhibited MACC1 expression in a time- and dose-dependent manner.
  • IFN-γ treatment reduced pancreatic cancer cell proliferation, migration, and invasion, and downregulated phosphorylated AKT and mTOR (pho-AKT, pho-mTOR).
  • Overexpression of MACC1-AS1 reversed these effects, while MACC1 silencing mimicked IFN-γ's inhibitory actions, with rescue assays confirming the pathway's involvement.

Conclusions:

  • IFN-γ exerts its anti-pancreatic cancer effects through the MACC1-AS1/MACC1 axis, modulating the AKT/mTOR signaling pathway.
  • The MACC1-AS1/MACC1 axis represents a novel therapeutic target for pancreatic cancer.
  • Understanding this mechanism provides new insights for developing targeted therapies for PC.
Keywords:
AKT/mTOR pathwayInterferon gamma (IFN-γ)MACC1MACC1-AS1Pancreatic cancer (PC)

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