Breast cancer cause highest number of deaths globally and is the most common type of cancer among women [
20,
21]. The development of new treatments is halted mainly because of drug resistance and less knowledge about tumor cell signaling pathways. Over the past decade, a class of small, non-coding, single-stranded RNAs known as miRNAs has emerged as major regulators of the initiation and progression of human cancers, including breast cancer [
22,
23]. Importantly, dysregulated and dysfunctional miRNAs play a causal role in cancer etiology because miRNAs can affect the translation and stability of targeted oncogenes and tumor suppressors, which eventually influences cellular physiology [
4‐
6]. In the present study, we detected significant reduction of miR-124-3p in breast cancer tissues. As one of the most enriched miRNAs in the brain of mammals [
24], miR-124-3p is involved in both brain development and neuronal function [
25,
26]. Recently, miR-124-3p has been identified as a tumor suppressor in some cancers, including hepatocellular carcinoma [
27], cervical cancer [
28] and gastric cancer [
29]. However, the function of miR-124-3p in breast cancer is largely unknown. In the present study, we found that miR-124-3p can suppress the proliferation and invasion of breast cancer cells, suggesting that miR-124-3p may play a critical role in the negative regulation of growth and metastasis of breast cancer. Accumulating evidence suggests that proliferation and invasion of cells are very important in carcinogenesis and its progression [
30]. The results indicate that miR-124-3p may serve as an ideal therapeutic target for breast cancer. Additional work is needed to characterize the feasibility of targeting miR-124-3p in cancer therapy and develop simplified and cost-effective methods.
The CBL families are highly conserved ubiquitin ligases. Thus far, three mammalian homologs have been defined — CBL (also known as c-CBL), CBL-b and CBL-c — which vary from one another on the basis of difference in length of C termini and their property to work as adaptors [
31]. Among the three homologs of the family, CBL is mainly known as a ubiquitin E3 ligase that is responsible for signal transduction in different cell types against various types of stimuli [
32,
33]. It is thought that the predominant function of CBL is causing ubiquitination of active RTKs thereby resulting in negative regulation of their signaling and directing them towards lysosomes to degrade [
34]. From this point of view, CBL may act mainly as a tumor suppressor in the pathogenesis of human cancers. For example, some studies revealed a role of CBL in restricting tumor cell proliferation and invasion [
35,
36]. Conversely, CBL is regarded as a proto-oncogene with numerous mutations and important roles in some cancers, including myeloid neoplasms [
37], colorectal cancer [
38] and glioma [
19]. Thus, if CBL acts as a tumor suppressor or an oncogene is dependent on the cell and tumor types. Under different circumstances, CBL may exert opposite functions. In breast cancer, the expression profile of CBL has not been systematically investigated and the precise function of this gene remains unclear. Overall, the findings of this study demonstrated that CBL is overexpressed in human breast cancer tissues and that the aberrant expression of CBL is responsible for the malignant behaviors of breast cancer cells. Consistently, it was reported that CBL blocks the tumor suppressor activity of TGF-β and enhances breast tumor formation [
17]. Furthermore, the molecular mechanism accounting for the aberrant upregulation of CBL in breast cancer was investigated. Mechanistic studies revealed that miR-124-3p directly binds the CBL 3’-UTR and inhibit CBL expression, and that CBL overexpression sufficiently attenuates the inhibitory effects of miR-124-3p on breast cancer cell proliferation and invasion. Therefore, the modulation of CBL by miR-124-3p may explain why the downregulation of miR-124-3p can promote the development of breast cancer.