MiR-1268b confers chemosensitivity in breast cancer by targeting ERBB2-mediated PI3K-AKT pathway

Abstract

Chemoresistance represents a major obstacle to effective therapy for breast cancer. Emerging evidences associated aberrantly expressed miRNAs with tumor development and chemoresistance. MiR-1268b has never been studied in any cancers before, and its roles in mediating tumor progression and drug resistance are still unclear. Selected from miRNA microarray and confirmed by real-time quantitative PCR (RT-qPCR), miR-1268b was found to be significantly upregulated in drug sensitive and ERBB2 negative tissues, as well as in breast cancer patients with low clinical stage. And miR-1268b had a higher expression in chemosensitive breast cancer cell lines, compared with the chemoresistant cell line. Moreover, the results revealed that miR-1268b induced breast cancer cell apoptosis and increased cell chemosensitivity. ERBB2 was demonstrated to be the target gene of miR-1268b by dual-luciferase reporter assays, western blot, and immunocytochemistry. Furthermore, PI3KCA, AKT, BCL2 in the ERBB2-PI3K-AKT signaling pathway were found to be downstream effectors of miR-1268b. In conclusion, miR-1268b increased chemosensitivity, at least in part, via modulation of PI3K-AKT pathway by targeting ERBB2. MiR-1268b may serve as a potential therapeutic target for patients with breast cancers.

A miRNA-based diagnostic model predicts resectable lung cancer in humans with high accuracy

“…To date, the function and serum expression profiles of these two miRNAs have not been extensively investigated. Zhu et al reported that miR-1268b is upregulated in drug-sensitive breast cancer, and that ERBB2, a receptor tyrosine kinase, is a direct target gene of miR-1268b 25 . On the other hand, Kojima et al reported that serum miR-6075 can detect pancreatic and biliary tract cancer with a sensitivity and specificity of 63.6 and 93.5%, respectively; their study analyzed 571 serum samples, including material from 100 patients with pancreatic or biliary tract cancer 26 .…”

Baicalin modulates NF-κB and NLRP3 inflammasome signaling in porcine aortic vascular endothelial cells Infected by Haemophilus parasuis Causing Glässer’s disease

“…The fluorescence intensities were then determined using a fluorescence microplate reader (Olympus, Japan). Apoptosis was detected using FITC Annexin V Apoptosis Detection Kit I (BD Pharmingen, USA) according to standard procedures, and examined by flow cytometry 76 . Briefly, 2 × 10 5 PAVECs were seeded into 24-well plates (Costar) and then treated with baicalin at a final concentration of 12.5, 25, 50, or 100 μg/mL, respectively, for 1 h. H. parasuis at 2 × 10 5 CFU/mL was then added into the plates and co-cultured for 12 h. The incubations were then washed three times with sterile phosphate-buffered saline and stained with FITC Annexin V and Propidium Iodide (PI).…”

Transcriptional Profiling of Host Cell Responses to Virulent Haemophilus parasuis: New Insights into Pathogenesis

“…Knockdown of HMGN5 could increase the chemosensitivity of human urothelial bladder cancer cells to cisplatin by targeting PI3K/Akt signaling [ 28 ]. miR-1268b increases breast cancer cell chemosensitivity via modulation of the PI3K/Akt pathway by targeting ERBB2 [ 29 ]. The PI3K/Akt pathway has also become an important contributor to cardiovascular disease due to its role in cardiac growth, angiogenesis, and cardiac hypertrophy [ 30 ].…”