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CCL21 activation of the MALAT1/SRSF1/mTOR axis underpins the development of gastric carcinoma

Qianmei Fu1,2, Xiaohong Tan1,2, Huaming Tang3,4

  • 1Oncology Department, The People's Hospital of Kaizhou District, Chongqing, 405400, People's Republic of China.

Journal of Translational Medicine
|May 18, 2021
PubMed
Abstract

Insights

Cytokine CCL21 promotes gastric cancer (GC) progression by upregulating MALAT1, SRSF1, and mTOR. This discovery offers a new therapeutic target for treating this fatal malignancy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Gastric carcinoma (GC) is a leading cause of cancer mortality with limited effective treatments.
  • Immunotherapy presents a promising strategy for cancer treatment by harnessing the immune system.
  • Understanding the molecular mechanisms driving GC progression is crucial for developing novel therapies.

Purpose of the Study:

  • To investigate the role of cytokine C-C motif chemokine ligand 21 (CCL21) in gastric cancer progression.
  • To elucidate the involvement of the metastasis-associated lung adenocarcinoma transcript 1/serine arginine-rich splicing factor 1/mammalian target of rapamycin (MALAT1/SRSF1/mTOR) axis in GC.
  • To identify potential therapeutic targets for GC treatment.

Main Methods:

  • Bioinformatics analysis to identify key genes and downstream targets in GC.
  • In-vitro and in-vivo experiments assessing the effects of CCL21, MALAT1, and SRSF1 on GC cell phenotypes and tumorigenesis.
  • RNA pull-down and immunoprecipitation assays to determine molecular interactions, including the MALAT1-miR-202-3p and miR-202-3p-SRSF1 pathways.

Main Results:

  • CCL21 was identified as a key immune gene in GC, with its overexpression correlating with GC progression.
  • Overexpression of CCL21, MALAT1, and SRSF1, and underexpression of miR-202-3p were observed in GC cells.
  • CCL21 promoted GC cell malignant phenotypes and epithelial-mesenchymal transition (EMT) by upregulating MALAT1, which in turn increased SRSF1 expression and activated the mTOR pathway.

Conclusions:

  • CCL21 enhances gastric cancer progression through the MALAT1/SRSF1/mTOR signaling axis.
  • The identified pathway represents a novel therapeutic target for gastric cancer.
  • Targeting the CCL21-MALAT1-SRSF1-mTOR pathway could offer a new strategy for GC treatment.
Keywords:
C–C motif chemokine ligand 21Gastric carcinomaMammalian target of rapamycinMetastasis-associated lung adenocarcinoma transcript-1Serine arginine-rich splicing factor 1

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