Downregulation of miR-135b-5p Suppresses Progression of Esophageal Cancer and Contributes to the Effect of Cisplatin

Yuzhu Di; Yanan Jiang; Xiuyun Shen; Jing Liu; Yang Gao; Huimin Cai; Xiaoli Sun; Dandan Ning; Bing Liu; Jiaji Lei; Shizhu Jin

doi:10.3389/fonc.2021.679348

Downregulation of miR-135b-5p Suppresses Progression of Esophageal Cancer and Contributes to the Effect of Cisplatin

Front Oncol. 2021 Jul 1:11:679348. doi: 10.3389/fonc.2021.679348. eCollection 2021.

Authors

Yuzhu Di¹, Yanan Jiang^{2

3}, Xiuyun Shen², Jing Liu¹, Yang Gao¹, Huimin Cai¹, Xiaoli Sun¹, Dandan Ning¹, Bing Liu³, Jiaji Lei⁴, Shizhu Jin¹

Affiliations

¹ Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
² Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.
³ Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China.
⁴ Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract

Esophageal cancer (EC) is one of the commonest human cancers, which accompany high morbidity. MicroRNAs (miRNAs) play a pivotal role in various cancers, including EC. Our research aimed to reveal the function and mechanism of miR-135b-5p. Our research identified that miR-135b-5p was elevated in EC samples from TCGA database. Correspondingly real-time PCR assay also showed the miR-135b-5p is also higher expressed in Eca109, EC9706, KYSE150 cells than normal esophageal epithelial cells (Het-1A). CCK8, Edu, wound healing, Transwell assay, and western blot demonstrated miR-135b-5p inhibition suppresses proliferation, invasion, migration and promoted the apoptosis in Eca109 and EC9706 cells. Moreover, the miR-135b-5p inhibition also inhibited xenograft lump growth. We then predicted the complementary gene of miR-135b-5p using miRTarBase, TargetScan, and DIANA-microT. TXNIP was estimated as a complementary gene for miR-135b-5p. Luciferase report assay verified the direct binding site for miR-135b-5p and TXNIP. Real-time PCR and western blot assays showed that the inhibition of miR-135b-5p remarkably enhanced the levels of TXNIP in Eca109 and EC9706 cells. Furthermore, cisplatin (cis-diamminedichloroplatinum II, DDP) decreased miR-135b-5p expression and increased TXNIP expression. Enhanced expression of miR-135b-5p attenuated the inhibitory ability of cisplatin (cis-diamminedichloroplatinum II, DDP) in Eca109 cells, accompanied by TXNIP downregulation. In conclusion, the downregulation of miR-135b-5p suppresses the progression of EC through targeting TXNIP. MiR-135b-5p/TXNIP pathway contributes to the anti-tumor effect of DDP. These findings may provide new insight into the treatment of EC.

Keywords: cisplatin; esophageal cancer; miR-135b-5p; proliferation; thioredoxin interacting protein.