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. This objective of this 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 epsilon (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 (Bax, 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 downregulated while PRKCE was upregulated 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.

中文翻译：

---

microRNA-205-5p的过表达通过下调PRKCE对胆囊癌干细胞耐药性产生抑制作用。

据报道，某些微RNA（miR或miRNA）在胆囊癌（GBC）中起抑癌作用。但是，miR-205-5p对GBC的特异性作用仍不清楚。这项研究的目的是揭示miR-205-5p对GBC耐药性的影响。为此，在从GBC患者和健康志愿者那里采集的外周血样本中对miR-205-5p和蛋白激酶Cε（PRKCE）的表达进行了定量。然后验证了miR-205-5p与PRKCE之间的关系。分离GBC干细胞后，进行异位表达和耗竭实验，以分析miR-205-5p和PRKCE对细胞增殖，耐药性，细胞凋亡和集落形成率以及凋亡因子（Bax， Bcl-2和裂解的caspase 3）。最后，建立了GBC的小鼠异种移植模型以验证miR-205-5p的体内功能。有趣的是，我们的结果表明，GBC患者的外周血样本和干细胞中miR-205-5p被下调，而PRKCE被上调。而且，miR-205-5p靶向PRKCE并对其表达负调控。miR-205-5p的过表达或PRKCE的沉默抑制了耐药性，增殖和集落形成速率，同时促进了GBC干细胞的凋亡。另外，miR-205-5p的过表达减弱了对吉西他滨的耐药性，但通过抑制体内PRKCE促进了吉西他滨诱导的细胞凋亡。总体而言，miR-205-5p与PRKCE之间的密切关系是GBC干细胞耐药性的关键决定因素。从而，