MiR-125b Functions as a Tumor Suppressor and Enhances Chemosensitivity to Cisplatin in Osteosarcoma

Abstract

Copyright: Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Numerous studies have shown drug resistance of gastric cancer cells could be modulated by abnormal expression of microRNAs. Cisplatin (DDP) is one of the most commonly used drugs for chemotherapy of gastric cancer. In this study, the potential function of miR-125b on DDP resistance in gastric cancer cells was investigated. Sixteen miRNAs significantly differential expressed in gastric tumor tissues and adjacent tissues were characterized and their corresponding putative target genes were also screened. MiR-125b was selected as our focus for its evident down-regulated expression among candidate genes. Real-time polymerase chain reaction assay indicated that miR-125b was significantly down-regulated in gastric cancer tissues and various cell lines. HER2 was identified as a target gene of miR-125b by dual luciferase reporter assay and Western blot. Moreover, miR-125b overexpression inhibited not only the proliferation, migration, and invasion abilities of HGC-27 and MGC-803 cells, but also in vivo tumor growth of MGC-803 cells by an intratumoral delivery approach. Notably, we observed up-regulated miR-125b contributed to the chemosensitivity of DDP in HGC-27 and MGC-803 cells at different concentrations and also possessed sensibilization for DDP at different times. MiR-125b expression was found to be related to lymph node metastasis, HER2 expression and overall survival of patients through correlation analysis. Collectively, these results indicate miR-125b may regulate DDP resistance as a promising therapeutic target for gastric cancer treatment in future. www.impactjournals.com/oncotarget/

Aberrantly expressed microRNAs in bladder cancer and renal cell carcinoma

“…26-29 miR-125b functions as a tumor suppressor in ovarian cancer, breast cancer, osteosarcoma and bladder cancer. [26][27][28][29][30][31][32] However, in prostate cancer, glioma and leukemia, miR-125b functions as an oncogene by targeting tumor suppressors. [33][34][35] miR-143-3p, miR-145-5p and miR-145-3p are clustered on chromosome 5q32, and multiple signatures have shown that these miRNAs are downregulated in BC.…”

Association of circulating miR-125b and survival in patients with osteosarcoma–A single center experience

“…Growing evidence indicates that various miRNAs (including miR-92a, miR-99b, miR-132, miR-193a-5p, miR-422a, and miR-125b) are involved in the development of resistance to chemotherapy [5], [9], [10]. It is thought that miR-125b can act as both an oncogene and a tumor suppressor, depending on the cellular context [11], [12], [13].…”

miR-125b is associated with renal cell carcinoma cell migration, invasion and apoptosis

“…A number of studies about miR-125b indicated that miR-125b acted as a tumor suppressor in osteosarcoma, ovarian cancer, hepatocellular carcinoma (HCC) and gastric cancer (15,(24)(25)(26). In ovarian cancer, miR-125a and miR-125b could inhibit ovarian cancer cell migration, invasion and proliferation by regulating EIF4E-binding protein 1 (24).…”

“…Thus, miR-125b may be used as a biomarker for gastric cancer (26). Wang et al (15) revealed that tumor suppressive miR-125b could negatively regulate osteosarcoma cell proliferation, invasion and migration, and that overexpression of miR-125b enhanced the chemosensitivity of osteosarcoma cells to cisplatin by targeting Bcl-2. Another study revealed that low expression of miR-125b in osteosarcoma predicted a poor prognosis (12).…”

“…The function of miR-125b in a number of cancer subtypes, including osteosarcoma and gastric cancer, was explored (15,16). In osteosarcoma, miR-125b was described as a tumor suppressor (15), and in gastric cancer, miR-125b functions as an oncogene (16).…”