MiR-376c-3p targets heparin-binding EGF-like growth factor (HBEGF) to inhibit proliferation and invasion in medullary thyroid carcinoma cells

Abstract

Introduction: Aggressive medullary thyroid carcinomas (MTC) have a high mortality rate and the treatment for patients diagnosed with advanced MTC is comparatively ineffective. We hence aimed to test the effects of miR-376c-3p on MTC and to explore the relevant mechanism. Material and methods: Cell Counting Kit-8 (CCK-8) and soft agar colony formation assay were applied to evaluate the proliferation of transfected MZ-CRC-1 cells. Wound healing and transwell assay were employed to evaluate MTC cell migration and invasion, respectively. Luciferase assay was performed to validate the downstream target of miR-376c-3p in MZ-CRC-1 cells. Quantitative polymerase chain reaction was used to detect mRNA abundance of key genes. Western blot technique was used to analyze protein levels of HBEGF, E-cadherin, ZO-1, N-cadherin and vimentin. Results: MiR-376c-3p inhibited the viability, migration and invasion of MZ-CRC-1 cells. Moreover, miR-376c-3p mimic downregulated expression of N-cadherin and vimentin but upregulated that of E-cadherin and ZO-1 in MZ-CRC-1 cells. Results for the luciferase reporter assay showed that miR-376c-3p was able to bind the 3′ untranslated region of heparin-binding EGF-like growth factor (HBEGF), of which overexpression nearly nullified the miR-376c-3p mimic-induced inhibitory effects in the MTC cells. Conclusions: MiR-376c-3p showed suppressive effects on MZ-CRC-1 cells via targeting and downregulating HBEGF, suggesting that miR-376c-3p could potentially be targeted for the treatment of MTC.

microRNA-194 is increased in polycystic ovary syndrome granulosa cell and induce KGN cells apoptosis by direct targeting heparin-binding EGF-like growth factor

“…3 ). HB-EGF stands out from all other potential target genes given its involvement in many other cancers, such as gliomagenesis [ 46 ], breast cancer [ 47 ], and medullary thyroid carcinoma [ 48 ]. In addition, previous studies also showed that HB-EGF mediates proliferation and apoptosis [ 49 ].…”

Topical Application of Cell-Penetrating Peptide Modified Anti-VEGF Drug Alleviated Choroidal Neovascularization in Mice

“…Previous reports utilized CCK-8 cell viability assays to assess the safety of the three at the cellular level. 39 We utilized ARPE-19 cells and HUVECs, commonly encountered at CNV lesion sites, to observe the cytotoxicity of 5-FITC-CPP, 5-FCR, and 5-FCC. Post-intervention, there were no significant changes in cell morphology or activity compared to the control group, displaying results similar to those in Vives et al’s study.…”

Investigation of ZIP4, ZO-1, and CLAUDIN-1 expression in thyroid tumours by immunohistochemistry and real-time polymerase chain reaction methods

“…Bai et al [24] reported a decrease in the expression of N-cadherin and Vimentin, and an increase in the expression of E-cadherin and ZO-1 with miR-376c-3p transfer, which reduces tumour aggressiveness and invasiveness in MTC cell lines. Thus, they demonstrated the protective effect of ZO-1 against tumour invasiveness.…”