Miao Xiang, Liu Yixiang, Fan Yuzhu, Wang Guoqiang, Zhu Hongbo
Department of General Surgery, Lianyungang Municipal Oriental Hospital, Lianyungang, Jiangsu 222042, People's Republic of China.
Cancer Manag Res. 2021 Jan 12;13:287-296. doi: 10.2147/CMAR.S269679. eCollection 2021.
Chemotherapy-based comprehensive treatments are the most important therapeutic methods for patients with advanced gastric cancer, but chemoresistance often cause treatment failure. Long non-coding RNA (LncRNA) BRAF-activated non-coding RNA (BANCR) has been shown to participate in many biological behaviors of multiple cancers. However, the biological roles of LncRNA BANCR in chemoresistance of gastric cancer remain unclear. Here, we aimed to evaluate the functions of LncRNA BANCR on the therapy of gastric cancer.
In this study, LncRNA BANCR expression was detected in gastric cancer patient samples and cell lines by quantity polymerase chain reaction (qPCR). Cell proliferation and viability in cisplatin-treated cells were measured using clonogenic survival assay and cell counting kit-8. The levels of ERK1/2 pathway molecules were tested with Western blot. Ly3214996, an inhibitor of ERK signal pathway, was administered to assess the effects of BANCR overexpression on gastric cancer cell with cisplatin-treated resistance. Moreover, the role of BANCR in cisplatin resistance of gastric cancer was validated in xenograft mouse models in vivo.
Our study revealed that LncRNA BANCR expression was also significantly increased in gastric cancer tissues compared with adjacent normal tissues. Furthermore, we found that BANCR overexpression promoted gastric cancer cell resistance to cisplatin in vitro. Ly3214996 treatment abolished the BANCR overexpression-mediated gastric cancer cell cisplatin resistance via regulating the phosphorylation of ERK protein. Knock-down of BANCR significantly delayed tumor growth in xenograft mouse models.
BANCR promoted cisplatin resistance of gastric cancer cells by activating ERK1/2 pathway. Inhibition of BANCR markedly suppressed the growth of gastric cancer cells in vitro as well as in vivo. These results provided a new strategy for gastric cancer therapy via targeting BANCR.
基于化疗的综合治疗是晚期胃癌患者最重要的治疗方法，但化疗耐药常导致治疗失败。长链非编码RNA（LncRNA）BRAF激活非编码RNA（BANCR）已被证明参与多种癌症的许多生物学行为。然而，LncRNA BANCR在胃癌化疗耐药中的生物学作用仍不清楚。在此，我们旨在评估LncRNA BANCR在胃癌治疗中的功能。
在本研究中，通过定量聚合酶链反应（qPCR）检测胃癌患者样本和细胞系中LncRNA BANCR的表达。使用克隆形成存活试验和细胞计数试剂盒-8测量顺铂处理细胞中的细胞增殖和活力。用蛋白质免疫印迹法检测ERK1/2信号通路分子的水平。给予ERK信号通路抑制剂Ly3214996，以评估BANCR过表达对顺铂处理耐药的胃癌细胞的影响。此外，在体内异种移植小鼠模型中验证了BANCR在胃癌顺铂耐药中的作用。
我们的研究表明，与相邻正常组织相比，LncRNA BANCR在胃癌组织中的表达也显著增加。此外，我们发现BANCR过表达促进了胃癌细胞在体外对顺铂的耐药性。Ly3214996处理通过调节ERK蛋白的磷酸化消除了BANCR过表达介导的胃癌细胞顺铂耐药性。在异种移植小鼠模型中敲低BANCR显著延迟了肿瘤生长。
BANCR通过激活ERK1/2信号通路促进胃癌细胞的顺铂耐药性。抑制BANCR在体外和体内均显著抑制了胃癌细胞的生长。这些结果为通过靶向BANCR治疗胃癌提供了一种新策略。
