Loss of miR‐6844 alters stemness/self‐renewal and cancer hallmark(s) markers through CD44‐JAK2‐STAT3 signaling axis in breast cancer stem‐like cells

Abstract

AbstractMicroRNAs regulate breast stemness and self‐renewal properties in breast cancer cells at the molecular level. Recently we reported the clinical relevance and in vitro expression profile of novel miR‐6844 in breast cancer and ‐derived stem‐like cells (mammosphere). In the present study, we first time explore the functional role of loss of miR‐6844 in breast cancer cells derived mammosphere. Down expression of miR‐6844 significantly decreased cell proliferation in MCF‐7 and T47D cells derived mammosphere in a time‐dependent manner. MiR‐6844 down expression reduced the sphere formation in terms of size and number in test cells. Loss of miR‐6844 significantly altered stemness and self‐renewal markers (Bmi‐1, Nanog, c‐Myc, Sox2, and CD44) in mammosphere compared to negative control spheres. Moreover, loss of miR‐6844 inhibits the JAK2‐STAT3 signaling pathway by decreasing p‐JAK2 and p‐STAT3 levels in breast cancer cells derived mammosphere. Loss of miR‐6844 expression significantly decreased CCND1 and CDK4 mRNA/protein levels and arrested breast cancer stem‐like cells in G2/M phase. Reduced expression of miR‐6844 increased Bax/Bcl‐2 ratio, late apoptotic cell population, and Caspase 9 and 3/7 activity in the mammosphere. Low expression of miR‐6844 decreased migratory and invasive cells by altering the expression of Snail, E‐cad, and Vimentin at mRNA/protein levels. In conclusion, loss of miR‐6844 decreases stemness/self‐renewal and other cancer hallmark in breast cancer stem‐like cells through CD44‐JAK2‐STAT3 axis. Thus, downregulation of miR‐6844 by therapeutic agents might be a novel strategy to target breast cancer stemness and self‐renewal.