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KIAA1429 regulates cell proliferation by targeting c-Jun messenger RNA directly in gastric cancer

Ran Miao1, Cong-Cong Dai1, Lin Mei2

  • 1Department of General Surgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.

Journal of Cellular Physiology
|February 14, 2020
PubMed

Insights

KIAA1429 acts as an oncogene in gastric cancer by stabilizing c-Jun mRNA independently of m6A modification. Upregulated KIAA1429 promotes cancer proliferation, suggesting it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • N6-methyladenosine (m6A) modification regulatory proteins are implicated in various cancers.
  • KIAA1429 functions as a scaffold protein within the m6A methyltransferase complex.
  • The specific role and mechanism of KIAA1429 in gastric cancer remain largely unexplored.

Purpose of the Study:

  • To investigate the role of KIAA1429 in gastric cancer development and progression.
  • To elucidate the underlying molecular mechanism of KIAA1429 action in gastric cancer.
  • To evaluate KIAA1429 as a potential prognostic biomarker and therapeutic target for gastric cancer.

Main Methods:

  • Quantitative real-time PCR and Western blot to assess KIAA1429 expression in gastric cancer tissues and cell lines.
  • In vitro (cell counting, colony formation, flow cytometry) and in vivo (nude mouse xenografts) assays to evaluate proliferation.
  • High-throughput sequencing, RNA immunoprecipitation (RIP), luciferase assays, and rescue experiments to identify KIAA1429 targets and mechanisms.

Main Results:

  • KIAA1429 was found to be upregulated in gastric cancer tissues compared to adjacent tissues.
  • Overexpression of KIAA1429 promoted gastric cancer cell proliferation in vitro and in vivo.
  • KIAA1429 was identified to stabilize c-Jun mRNA in an m6A-independent manner, and c-Jun overexpression rescued proliferation inhibition upon KIAA1429 knockdown.

Conclusions:

  • KIAA1429 functions as an oncogene in gastric cancer by stabilizing c-Jun mRNA through an m6A-independent mechanism.
  • KIAA1429 promotes gastric cancer proliferation.
  • KIAA1429 represents a promising prognostic biomarker and therapeutic target for gastric cancer.
Keywords:
KIAA1429c-Jungastric cancerm6A independent manner

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