miR-338-5p modulates growth and chemoresistance of esophageal cancer cell via targeting FERRMT2

Esophageal cancer is the 5th leading cause of cancer death among male population in Eastern Asia. The esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Taiwan. Due to the poor overall 5-year survival rate, effective treatment strategies are required to improve the long-term survival rate. miRNAs are important gene regulators that may be dysregulated in many cancer types. The expression level of miR-338-5p was found to be downregulated in esophageal tumor tissues compared to the adjacent nontumor tissues. However, the functions and the potential target genes of miR-338-5p in ESCC are still unclear. In this study, we transfected miR-338-5p mimic into the ESCC cell line, CE-81T/VGH, which expresses low levels of miR-338-5p. The results showed that miR-338-5p mimic can inhibit cell proliferation, migration, and colony formation. In order to identify the target genes of miR-338-5p, microarray analysis was performed to select significantly downregulated genes in the miR-338-5p mimic transfected CE-81T/VGH cells. Moreover, miRSystem was used to predict the miR-338-5p putative target genes. By cross-comparing the results from the microarray and miRSystem analysis, FERMT2 was identified as the most likely candidate gene, and it was validated by real-time PCR. The function of FERMT2 was further studied in the CE-81T/VG cell. Silencing of FERMT2 can inhibit cell proliferation, migration, and colony formation in the ESCC cells. The luciferase activity assays results showed the direct binding between miR-338-5p and 39UTR region of FERMT2. To further confirm that miR-338-5p can go through FERMT2 to regulate cell functions, the “rescue” experiments were performed. As the results, overexpression of FERMT2 after miR-338-5p mimic transfection could restore cell migration and cell proliferation. Moreover, it has been reported that FERMT2 can increase chemoresistance in glioma cells. Therefore, the effects of miR-338-5p and FERMT2 on drug resistance were studied, and the results showed that miR-338-5p mimic transfection or FERMT2 silencing can increase cisplatin-induced cytotoxicity in the CE-81T/VGH cells. These data indicated that miR-338-5p can inhibit cell proliferation, migration, colony formation, and enhance cisplatin sensitivity in the ESCC cells by targeting FERMT2 expression. Therefore, miR-338-5p plays an important role in the ESCC cells via repressing FERMT2 and it could be used as a new research target for cancer treatment. Citation Format: Wen-chun Lin, Yao-chin Hsieh, Li-han Chen, Pei-wen Yang, Chi-Cheng Huang, Liang-chuan Lai, Jang-ming Lee, Eric Yao-yu Chuang, Mong-hsun Tsai. miR-338-5p modulates growth and chemoresistance of esophageal cancer cell via targeting FERRMT2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4432.