RAI14 silencing suppresses progression of esophageal cancer via the STAT3 pathway

Jianlin Wang1,2,3, Yun Cai4, Judong Luo3

  • 1Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China.

Aging
|September 21, 2020
PubMed

Insights

Retinoic acid induced 14 (RAI14) acts as an oncogene in esophageal cancer (EC). Upregulation of RAI14 promotes EC cell growth and invasion by activating the STAT3 pathway, indicating its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Esophageal cancer (EC) is an aggressive malignancy with poorly understood molecular mechanisms.
  • The role of retinoic acid induced 14 (RAI14) in EC progression remains unclear.

Purpose of the Study:

  • To investigate the function and molecular mechanisms of RAI14 in esophageal cancer.
  • To determine the correlation between RAI14 expression and clinical outcomes in EC patients.

Main Methods:

  • Analysis of TCGA database for RAI14 expression in EC.
  • In vitro studies using EC cell lines to assess the effects of RAI14 overexpression and knockdown on cell behavior (proliferation, migration, invasion, apoptosis, cell cycle).
  • In vivo studies involving tumor xenografts to evaluate the impact of RAI14 silencing on tumor growth.

Main Results:

  • RAI14 was found to be upregulated in EC, correlating with advanced T stage, higher histologic grade, and poorer prognosis.
  • RAI14 overexpression enhanced EC cell proliferation, migration, and invasion, while knockdown induced apoptosis and cell cycle arrest.
  • RAI14 activated the STAT3 pathway, leading to increased Mcl-1 and cyclin D1 levels and decreased cleaved caspase-3.
  • STAT3 inhibition reversed the oncogenic effects of RAI14, and RAI14 silencing suppressed tumor growth and Ki67 expression in vivo.

Conclusions:

  • RAI14 functions as an oncogene in esophageal cancer progression.
  • RAI14 promotes EC tumorigenesis by regulating the STAT3 signaling pathway.
  • RAI14 represents a potential therapeutic target for esophageal cancer treatment.

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