Knockdown of CSNK2ß suppresses MDA-MB231 cell growth, induces apoptosis, inhibits migration and invasion.

Knockdown of CSNK2ß suppresses MDA-MB231 cell growth, induces apoptosis, inhibits migration and invasion.:



Knockdown of CSNK2ß suppresses MDA-MB231 cell growth, induces apoptosis, inhibits migration and invasion.

EXCLI J. 2020;19:1211-1226

Authors: Karna SKL, Lone BA, Ahmad F, Shahi N, Pokharel YR

Abstract

Breast cancer is the most common cancer among women worldwide. Among different types of breast cancer known, treatment of triple-negative breast cancer is a major challenge because of its aggressiveness and poor prognosis; thus, identification of specific drivers is required for targeted therapies of breast cancer malignancy. Protein Casein Kinase (CSNK) is a serine/threonine kinase that exists as a tetrameric complex consisting of two catalytic (α and /or α') and two regulatory β subunits. CSNK2β can also function independently without catalytic subunits and exist as a distinct population in cells. This study aims to elucidate the role of Casein Kinase 2β (CSNK2β) gene in cell proliferation, cell cycle, migration and apoptosis of triple-negative breast cancer MDA-MB-231 cells. The silencing of CSNK2β in MDA-MB-231 cells resulted in decreased cell viability and colony formation. Cell cycle analysis showed a significant arrest of cells in G2M phase. Hoechst and CM-H2DCFDA staining showed nuclear condensation and augmented intracellular reactive oxygen species (ROS) production. Furthermore, silencing of CSNK2β in MDA-MB-231 cells modulated the apoptotic machinery- BAX, Bcl-xL, and caspase 3; autophagy machinery-Beclin-1 and LC3-1; and inhibited the vital markers (p-ERK, c-Myc, NF-κB, E2F1, PCNA, p38-α) associated with cell proliferation and DNA replication pathways. In addition, knockdown of CSNK2β also affected the migration potential of MDA-MB-231, as observed in the wound healing and transwell migration assays. Altogether, the study suggests that CSNK2β silencing may offer future therapeutic target in triple-negative breast cancer.



PMID: 33013272 [PubMed]