Overexpression of microRNA-205-5p exerts suppressive effects on stem cell drug resistance in gallbladder cancer by down-regulating PRKCE. Issue 9 (29th September 2020)

• Record Type: Journal Article
• Authors: Zhang, Guo-Feng; Wu, Jia-Cheng; Wang, Hong-Yong; Jiang, Wei-Dong; Qiu, Ling
• Is Part Of: Bioscience reports. Volume 40:Issue 9(2020)
• Publication Date: 2020-09-29
• Subjects: Apoptosis -- Drug resistance -- Gallbladder cancer -- miR-205-5p -- PRKCE -- Proliferation; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20194509
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract: Some microRNAs (miRs or miRNAs) have been reported to function as tumor suppressors in gallbladder cancer (GBC). However, the specific effect of miR-205-5p on GBC remains unclear. The objective of the present study was to unravel the effects of miR-205-5p on the drug resistance in GBC. For this purpose, the expression of miR-205-5p and protein kinase C ϵ (PRKCE) was quantified in the peripheral blood sample harvested from GBC patients and healthy volunteers. Then the relationship between miR-205-5p and PRKCE was validated. After isolating the GBC stem cells, ectopic expression and depletion experiments were conducted to analyze the effect of miR-205-5p and PRKCE on cell proliferation, drug resistance, apoptosis, and colony formation rate as well as the expression of apoptotic factors (Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and cleaved caspase 3). Finally, the mouse xenograft model of GBC was established to verify the function of miR-205-5p in vivo . Intriguingly, our results manifested that miR-205-5p was down-regulated, while PRKCE was up-regulated in peripheral blood samples and stem cells of patients with GBC. Moreover, miR-205-5p targeted PRKCE and negatively regulated its expression. The overexpression of miR-205-5p or silencing of PRKCE inhibited the drug resistance, proliferation, and colony formation rate while promoting apoptosis of GBC stem cells. Additionally, the overexpression of miR-205-5p attenuated drug resistance to gemcitabine but promoted the gemcitabine-induced cell apoptosis by inhibiting the PRKCE in vivo . Overall, an intimate correlation between miR-205-5p and PRKCE is a key determinant of drug resistance of GBC stem cells, thus, suggesting a novel miR-205-5p-based clinical intervention target for GBC patients.