LncRNA BANCR Attenuates the Killing Capacity of Cisplatin on Gastric Cancer Cell Through the ERK1/2 Pathway
Received 27 June 2020
Accepted for publication 27 November 2020
Published 12 January 2021 Volume 2021:13 Pages 287—296
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Sanjeev Srivastava
Xiang Miao, Yixiang Liu, Yuzhu Fan, Guoqiang Wang, Hongbo Zhu
Department of General Surgery, Lianyungang Municipal Oriental Hospital, Lianyungang, Jiangsu 222042, People’s Republic of China
Correspondence: Hongbo Zhu
Department of General Surgery, Lianyungang Municipal Oriental Hospital, No. 57, Zhonghua West Road, Lianyungang, Jiangsu 222042, People’s Republic of China
Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: BANCR, chemoresistance, cisplatin, ERK1/2 pathway, gastric cancer