CCL21 activation of the MALAT1/SRSF1/mTOR axis underpins the development of gastric carcinoma
Authors: Qianmei Fu
Xiaohong Tan
Huaming Tang
Jijiang Liu
Journal: Journal of Translational Medicine (2021)
Discipline: CLINICAL MEDICINE
Keywords: C–C motif chemokine ligand 21; Gastric carcinoma; Mammalian target of rapamycin; Metastasis-associated lung adenocarcinoma transcript-1; Serine arginine-rich splicing factor 1.
Affiliations: Oncology Department, The People's Hospital of Kaizhou District, Chongqing, 405400, People's Republic of China., General Surgery Department, The People's Hospital of Kaizhou District, Chongqing, 405400, People's Republic of China., General Surgery Department, The People's Hospital of Kaizhou District, Chongqing, 405400, People's Republic of China. ., Department of Gastroenterology, The People's Hospital of Kaizhou District, No. 8, Ankang Road, Kaizhou District, Chongqing, 405400, People's Republic of China. ., Department of Otorhinolaryngology, The People's Hospital of Kaizhou District, No. 8, Ankang Road, Kaizhou District, Chongqing, 405400, People's Republic of China. .

Abstract:  Background: As a significant cause of malignancy mortality, gastric carcinoma (GC) has been well documented to be an often-fatal diagnosis. Despite the limitations of effective therapy, immunotherapy has emerged as a promising therapeutic approach capable of killing cancer cells via the immune system. The current study was conducted to investigate the effect of cytokine C-C motif chemokine ligand 21 (CCL21) on GC progression through the metastasis-associated lung adenocarcinoma transcript 1/serine arginine-rich splicing factor 1/mammalian target of rapamycin (MALAT1/SRSF1/mTOR) axis. Methods: Bioinformatics analysis was conducted to identify the key genes associated with GC and to subsequently predict their downstream genes. The effect of CCL21, MALAT1, and SRSF1 on the malignant phenotypes and epithelial-mesenchymal transition (EMT) of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo were assessed by expression determination and plasmid transfection. Additionally, RNA pull-down and RNA binding protein immunoprecipitation experiments were performed to determine the MALAT1-microRNA-202-3p (miR-203-3p) interaction and miR-202-3p-SRSF1 interaction followed by the analysis of their effect on the mTOR pathway. Results: CCL21 was identified as a key GC immune gene. Overexpressed CCL21, MALAT1, and SRSF1 along with poorly expressed miR-202-3p were identified in the GC cells. CCL21 induced the MALAT1 expression in a time- and dose-dependent manner. Functionally, MALAT1 targeted miR-202-3p but upregulated SRSF1 and activated mTOR. Crucially, evidence was obtained indicating that CCL21 promoted both the malignant phenotypes and EMT of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo by increasing the MALAT1-induced upregulation of SRSF1. Conclusions: Taken together, the key observations of our study provide evidence that CCL21 enhances the progression of GC via the MALAT1/SRSF1/mTOR axis, providing a novel therapeutic target for the treatment of GC. 

Retracted: No

PubPeer comments:
 This paper make uses of the following cell line  Human GC cell line SGC-7901 (American Type Culture Collection, ATCC, Manassas, VA, USA) . There are two problems: 1) ATCC has never distributed SGC-7901, si this statement is incorrect. 2) SGC-7901 is not a gastric carcinoma cell line, but is a HeLa contaminated cell line. Thus many of the conclusions of this paper when relevant to experiments carried out on SGC-7901 are unfortunatly not relevant. See the relevant [Cellosaurus entry] ,