MicroRNA 10b promotes abnormal expression of the proto-oncogene c-Jun in metastatic breast cancer cells

Abstract

MicroRNAs have been shown to act as oncogenes or tumor suppressers via various cellular pathways. Specifically, in breast cancer, upregulation of miR-10b is positively associated with aggressiveness of tumors. However, the mechanism by which miR-10b contributes to cell malignancy is largely unknown. Here we show that at the receiving end of the miR-10b pathway is the proto-oncogene c-Jun, a transcription factor that plays a critical role in stimulation of cell proliferation and tumor progression. c-Jun is known to be translationally activated by loss of cell contacts or restructuring of the cytoskeleton. A comprehensive analysis of miRNA expression exhibited a significant increase in miR-10b expression. This was supported by analysis of breast cancer cells, which showed that loss of E-cadherin in metastatic cells is accompanied by elevation of miR-10b and interestingly, by a marked increase in accumulation of c-Jun. Silencing miR-10b in metastatic breast cancer cells leads to a decline in c-Jun expression, whereas overexpression of miR-10b in HaCaT cells is sufficient to elevate the accumulation of c-Jun. The increase in c-Jun protein accumulation in metastatic cells is not accompanied by an increase in c-Jun mRNA and is not dependent on MAPK activity. Knockdown and overexpression experiments revealed that the increase is mediated by NF1 and RhoC, downstream targets of miR-10b that affect cytoskeletal dynamics through the ROCK pathway. Overall, we show the ability of miR-10b to activate the expression of c-Jun through RhoC and NF1, which represents a novel pathway for promoting migration and invasion of human cancer cells.

MicroRNA-10b Promotes Apoptosis via JNK Pathway in Clear Cell Renal Cell Carcinoma

“…Moreover, our data suggested a concurrent mode of action besides cell growth inhibitory effect of miR-10b. As previously proposed in metastatic breast cancer, miR-10b promoted the abnormal expression of proto-oncogene c-Jun and activation of MAPK pathway [27]. In line with this notion, our results indicated the activation of the JNK pathway other than ERK or p38 underlying cell apoptosis elicited by miR-10b.…”

Inhibition of miR‐148a‐3p resists hepatocellular carcinoma progress of hepatitis C virus infection through suppressing c‐Jun and MAPK pathway

“…They also pointed out the role of the mitogen‐activated protein kinase (MAPK) signalling pathways played in the activity of AP‐1 factors . Now, c‐Jun has been proved to have a regulation on proliferation, apoptosis, tumorigenesis and many other cell activities in various cancers . Previous study figured that c‐Jun mostly was a positive regulator in cell proliferation .…”

MicroRNA-10b mediates TGF-β1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition

“…As an oncogenic miRNA, miR-10b can regulate growth and metastasis of various types of cancer (13)(14)(15). miR-10b widely participated in the regulating of breast cancer proliferation and metastasis (42,43). However, miR-10b may play diverse roles in different tumors.…”