Eur Rev Med Pharmacol Sci 2021; 25 (11): 3967-3980
DOI: 10.26355/eurrev_202106_26037

Ribosomal protein RPS15A augments proliferation of colorectal cancer RKO cells via regulation of BIRC3, p38 MAPK and Chk1

B.-S. Wan, X.-Y. Wang, J. Tiang, C. Zhou, J. Lin, Z. Wang

Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China


OBJECTIVE: Ribosomal protein S15A (RPS15A) has been implicated in tumorigenesis, but its role in colorectal cancer (CRC) is not fully studied. The objective of this study was to investigate the role of RPS15A in CRC carcinogenesis.

PATIENTS AND METHODS: RBSP15A expression was detected in 120 colorectal adenocarcinoma biopsies by immunohistological staining, and we examined the association of RSP15A expression with clinicopathological outcomes. We generated RPS15A stable knockdown CRC cell lines using shRNAs and assessed cell proliferation by MTT assays, clonogenicity by colony formation assays, and apoptosis and cell cycle arrest by flow cytometric analyses. A mouse tumor xenograft model was used to confirm the influence of RPS15A expression on CRC in vivo.

RESULTS: RPS15A expression was predictive for poor disease-free survival. Knockdown of RPS15A expression significantly inhibited cell proliferation and colony formation and augmented apoptosis in both the RKO and SW620 CRC cell lines. Moreover, RPS15A knockdown arrested RKO cells at the G2/M phase and SW620 cells at the G0/G1 phase. KEGG pathway analysis of 785 genes differentially expressed between wild-type and shRPS15A RKO cells showed enrichment for the pathway in cancer and MAPK signaling pathway KEGG terms. RPS15A knockdown induced apoptosis via regulation of BIRC3, p38 MAPK, and Chk1. Consistently, RPS15A knockdown significantly impaired the growth of subcutaneous CRC xenografts in nude mice.

CONCLUSIONS: These results indicate that RPS15A is a novel, potentially oncogenic gene involved in colorectal carcinogenesis. RPS15A knockdown may be an attractive strategy for treating CRC with gene therapy.

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To cite this article

B.-S. Wan, X.-Y. Wang, J. Tiang, C. Zhou, J. Lin, Z. Wang
Ribosomal protein RPS15A augments proliferation of colorectal cancer RKO cells via regulation of BIRC3, p38 MAPK and Chk1

Eur Rev Med Pharmacol Sci
Year: 2021
Vol. 25 - N. 11
Pages: 3967-3980
DOI: 10.26355/eurrev_202106_26037