miR193a-5p Mediated ZNF746 and c-Myc Signaling Axis Is Critically Involved in Morusin Induced Apoptosis in Colorectal Cancer Cells

Cells

Hyo-Jung Lee¹  Bum-Sang Shim¹  Sung-Hoon Kim¹  Eunji Im¹  Deok-Yong Sim¹  Ji-Eon Park¹  Chi-Hoon Ahn¹  Woon-Yi Park¹ 

[1] Department of Korean Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea;

关键词: morusin;    colorectal cancer;    apoptosis;    ZNF746/c-Myc;    miR-193a-5p;   

DOI  :  10.3390/cells10082065

来源: DOAJ

【 摘 要 】

Novel target therapy is on the spotlight for effective cancer therapy. Hence, in the present study, the underlying apoptotic mechanism of Morusin was explored in association with miR193a-5p mediated ZNF746/c-Myc signaling axis in colorectal cancer cells (CRCs). Herein, Morusin reduced the viability and the number of colonies in HCT116 and SW480 CRCs. Additionally, Morusin increased sub-G1 population, cleavages of poly (ADP-ribose) polymerase (PARP) and caspase-3 and inhibited the expression of zinc finger protein 746 (ZNF746) and c-Myc in HCT116 and SW480 cells. Conversely, overexpression of ZNF746 suppressed the ability of Morusin to abrogate the expression of c-Myc in HCT116 cells, as ZNF746 enhanced the stability of c-Myc via their direct binding through nuclear colocalization in HCT116 cells by immunofluorescence and immunoprecipitation. Notably, Morusin upregulated miR193a-5p as a tumor suppressor, while miR193a-5p inhibitor masked the ability of Morusin to reduce the expression of ZNF746, c-Myc, and pro-PARP in HCT116 cells. To our knowledge, these findings provide the novel insight on miR193a-5p mediated inhibition of ZNF746/c-Myc signaling in Morusin induced apoptosis in CRCs.

【 授权许可】

Unknown