BCAR4 increase cisplatin resistance and predicted poor survival in gastric cancer patients

L. Wang, Q. Chunyan, Y. Zhou, Q. He, Y. Ma, Y. Ga, X. Wang

Department of Pharmacy, People’s Hospital of Yuxi City, Yuxi, Yunnan Province, China. wx300@163.com

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• Oncology

OBJECTIVE: Gastric cancer is a common malignancy with increasing worldwide incidence, and chemotherapeutic drugs for gastric cancer are not effective. Long non-coding RNA (lncRNA) has been proved to be important in different cancer progression. In this research, we investigated whether lncRNAs have relations with drug resistance in gastric cancer to find new potential targets for therapy, which can increase the survival time of the drug-resistant gastric patient.

PATIENTS AND METHODS: qRT-PCR was used to detect the expression of BCAR4 in 113 cases of gastric cancer tissue and adjacent tissue, and the clinical significance was also analyzed. MTT assays and Western blot were performed to cytologically determine the relationship between BCAR4 expression and cisplatin resistance, as well as to investigate the potential molecular mechanism involved.

RESULTS: Compared with the adjacent tissues, we found that BCAR4 was highly expressed in gastric cancer tissues. We also found that the expression of BCAR4 was significantly related to the size of the tumor, clinical classification and the survival time. In cytological experiments, we found the expression of BCAR4 was enhanced in cisplatin-resistant cell strains (SGC7901/DDP). What’s more, overexpression of BCAR4 in SGC7901 cells increased resistance to cisplatin while reduced BCAR4 expression increased the sensitivity of SGC7901/DDP cells to cisplatin. Western blot experiments indicated that elevated expression of BCAR4 upregulated tumor stem cell-related biomarkers via regulating Wnt signaling pathway.

CONCLUSIONS: We showed that BCAR4 was closely related with the cisplatin-resistant gastric cancer. It might be a promising target for treating gastric cancer and improving the efficiency of chemotherapeutic drugs.

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