miR-101 Promotes Breast Cancer Cell Apoptosis by Targeting Janus Kinase 2

Abstract

Aims: microRNA-101 (miR-101) is down-regulated in several cancers. In this study, we explored the effects of dysregulated miR-101 on breast cancer cells and the underlying mechanisms. Methods: miR-101 level was quantified by real-time RT-PCR. Cell viability was analyzed by MTT assay. Apoptosis was detected by flow cytometry and TUNEL assay. Moreover, the level of protein expression was determined by Western blot. Results: miR-101 level was markedly reduced in both the human breast cancer samples and cultured breast cancer cell lines (MCF-7, MDA-MB-231). Overexpression of miR-101 inhibited the proliferation and promoted the apoptosis in cultured MCF-7 and MDA-MB-231 cells, which were reversed by co-transfection of AMO-101, the inhibitor of miR-101. We validated Janus kinase 2 (Jak2) as a direct target of miR-101. Knockdown of Jak2 induced apoptosis in cultured breast cancer cells. Moreover, the level of miR-101 is negatively correlated with Jak2 in breast cancer tissues and cell lines. Conclusions: miR-101 suppressed proliferation and promoted apoptosis in breast cancer cells by targeting Jak2. These findings indicate that manipulation of miR-101 expression may represent a novel therapeutic strategy in the treatment of breast cancer.

The Role of Immune Modulatory MicroRNAs in Tumors

“…Thus, miRNA-135a may function as tumor suppressor by regulating JAK2 expression in gastric cancer cells [107]. Several studies confirmed other miRNAs targeting JAK2, including miRNA-216a, which is known to inhibit cell growth and promote apoptosis of pancreatic cancer cells by regulating JAK2/STAT3 signaling pathway [108,109], as well as miRNA-101, which promotes apoptosis of breast cancer cells by targeting JAK2 [110]. Similar results were found for STAT1 and miRNA-145 [111].…”

MicroRNA-101 protects cardiac fibroblasts from hypoxia-induced apoptosis via inhibition of the TGF-β signaling pathway

“…Bu et al (2014) reported that miR-101 enhanced cisplatin-induced apoptosis in human bladder cancer cells by modulating the cyclooxygenase-2 pathway. In addition, a study by Wang et al (2014) demonstrated that miR-101 induced apoptosis in breast cancer cells by targeting Janus Kinase 2. However, Zou et al (2014) found that miR-101 suppressed stressinduced trophoblast apoptosis by targeting ERp44.…”

Multiple Roles of MicroRNA-100 in Human Cancer and its Therapeutic Potential

“…Therefore, this therapy can reduce side effects in patients, since it avoids indiscriminately killing proliferating cells and instead concentrates its efficacy on cancer cells. Interfering with estrogen receptor (ER) activation is currently the gold standard for the treatment of breast cancer [147]. By promoting the expression of a functional ER, converting a basal like phenotype into luminal, miR-100 renders basal-like BrCSCs responsive to hormonal therapy [34].…”