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

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.

MicroRNA-135b-5p regulates trophoblast cell function by targeting phosphoinositide-3-kinase regulatory subunit 2 in preeclampsia

“…MiR-135b-5p overexpression alleviated the impairment of proliferation, migration, and invasion and promoted apoptosis induced by H/R. Furthermore, we observed the opposite effects after knockdown of miR-135b-5p, which is consistent with previous findings [ 40 , 41 , 54 ]. These findings indicate that miR-135b-5p may affect PE progression by regulating trophoblast cell function.…”

“…Another study has reported that the overexpression of miR-135b-5p promotes proliferation and reduces cell apoptosis by targeting Krüppel-like factor 4 in gastric cancer cells [ 54 ]. Conversely, miR-135b-5p knockdown suppresses proliferation and metastasis and facilitates the apoptosis of esophageal cancer cells via regulation of the thioredoxin-interacting protein (TXNIP) [ 40 ]. However, the role of miR-135b-5p in trophoblast function and PE has not been fully elucidated.…”

The role of miRNAs and lncRNAs in neurofibromatosis type 1

“…Therefore, these two revealed to silence the same target genes. 71,72 These two miRNAs have recently been shown to have a critical role in carcinogenesis and invasiveness in lung, 73 breast, 74 gastric, esophageal, 75 and pancreatic. 51 cancers.…”

microRNA-569 inhibits tumor metastasis in pancreatic cancer by directly targeting NUSAP1

“…MicroRNAs (miRNAs), containing 22 to 25 nucleotides, belong to single-stranded ribonucleic acid and exert function by degrading or inhibiting the translation of other proteins to regulate gene expression [ 7 ]. Dysregulation of miRNAs were closely associated with the occurrence of various diseases, especially cancers [ 8 – 12 ]. In lung cancer, miRNA-569 can be used as a tumor suppressor to induce apoptosis [ 13 ].…”