miR-199a-3p knockdown inhibits dedifferentiated liposarcoma (DDLPS) cell viability and enhances apoptosis through targeting casein kinase-1 alpha (CK1α)

• Published in: RSC advances 2019, Vol.9 (39), p.22755-22763
• Main Authors: Cao, Ye, Zheng, Jiajia, Lv, Chentao
• Format: Article
• Language: English
• Subjects: Antigens; Apoptosis; Casein; Flow cytometry; Gene expression; Kinases; Ribonucleic acid; RNA; Tumors; Xenotransplantation
• ISSN: 2046-2069
• DOI: 10.1039/c9ra01491h

Dedifferentiated liposarcoma (DDLPS) is an aggressive tumor with high mortality. More insight into the biology of DDLPS tumorigenesis is needed to devise novel therapeutic approaches. Previous data showed that miRNA-199a-3p (miR-199a-3p) was strongly upregulated in DDLPS tissues. However, the biological role of miR-199a-3p in DDLPS remains unknown. In this study, we detected miR-199a-3p expression using RT-qPCR and observed that miR-199a-3p was more highly expressed in DDLPS tissues and cell lines (SW872 and LPS141). Functionally, MTT assay, flow cytometry and western blot results demonstrated that knockdown of miR-199a-3p inhibited DDLPS cell viability, enhanced apoptosis rate, and decreased expression of apoptosis-related genes Bax and cleaved caspase 3, as well as increased Bcl-2 expression in vitro . Moreover, xenograft tumors were generated and miR-199a-3p knockdown could suppress DDLPS xenograft tumor growth accompanying decreased proliferating cell nuclear antigen (PCNA) level and increased cleaved caspase 3 level in vivo . Mechanically, luciferase reporter assay and RNA immunoprecipitation (RIP) identified that CK1α was targeted and downregulated by miR-199a-3p. Expression of CK1α was lower in DDLPS tissues. Besides, there was a negative linear correlation between expressions of miR-199a-3p and CK1α in DDLPS tissues. Rescue experiments indicated that CK1α silencing could abolish the effect of miR-199a-3p knockdown on cell viability and apoptosis in DDLPS cells in vitro . In conclusion, knockdown of miR-199a-3p inhibits DDLPS cell viability and enhances apoptosis through targeting CK1α in vitro and in vivo . Our results suggest miR-199a-3p/CK1α axis may be a novel pathogen of DDLPS. Dedifferentiated liposarcoma (DDLPS) is an aggressive tumor with high mortality.