Dataset Information

MiRNA-299-5p regulates estrogen receptor alpha and inhibits migration and invasion of papillary thyroid cancer cell.

ABSTRACT:

Background

The incidence of papillary thyroid cancer (PTC) is increasing faster than any other solid tumors worldwide. Invasion and metastasis are the main reasons for the poor prognosis of patients with PTC. Previously, we observed significantly low expression of miRNA-299-5p in invasive PTC tissue samples.

Aim

The present study aimed to determine whether miR-299-5p plays a key role in PTC migration and invasion.

Materials and methods

The miR-299-5p expression level was measured using quantitative real-time PCR in 109 human PTC samples and paired adjacent normal tissues and in the human BCPAP PTC cell line. The effects of miR-299-5p on PTC cell migration and invasion were assessed using wound healing and transwell assays. In addition, we searched for the miR-299-5p target, and the potential mechanism was demonstrated using a reporter assay and rescue experiment.

Results

The expression of miR-299-5p was associated with gender and extrathyroidal extension, and an elevated level of miR-299-5p suppressed BCPAP cell migration and invasion. Estrogen receptor ? (ER?) is a direct target of miR-299-5p. The expression level of ER? was significantly higher in PTC tissues and was associated with migration and invasion in PTC cells. Overexpression of ER? could impair miR-299-5p-induced inhibition of migration and invasion. As a key factor of the pathway related to PTC invasion, Gli1 can be combined with ER? and can be regulated by miR-299-5p.

Conclusion

Our data suggested that miR-299-5p could participate in PTC migration and invasion and could be a potential therapeutic target for patients with aggressive PTC tumors.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6257197 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

miRNA-299-5p regulates estrogen receptor alpha and inhibits migration and invasion of papillary thyroid cancer cell.

Wang Zhihong Z He Liang L Sun Wei W Qin Yuan Y Dong Wenwu W Zhang Ting T Zhang Ping P Zhang Hao H

Cancer management and research 20181122

<h4>Background</h4>The incidence of papillary thyroid cancer (PTC) is increasing faster than any other solid tumors worldwide. Invasion and metastasis are the main reasons for the poor prognosis of patients with PTC. Previously, we observed significantly low expression of miRNA-299-5p in invasive PTC tissue samples.<h4>Aim</h4>The present study aimed to determine whether miR-299-5p plays a key role in PTC migration and invasion.<h4>Materials and methods</h4>The miR-299-5p expression level was me ...[more]

PMID: 30538565

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Project description:IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that regulate genetic expression and are also vital for tumor initiation and development. MiR-29b-3p was found to be involved in regulating various biological processes of tumors, including tumor cell proliferation, metastasis, and apoptosis inhibition; however, the biofunction and molecule-level mechanisms of miR-29b-3p inpapillary thyroid carcinoma (PTC) remain unclear.MethodsThe expression of miR-29b-3p in PTC samples was tested via qRT-PCR. Cellular proliferation was analyzed by CCK-8 and EdU assays, and cellular migratory and invasive abilities were assessed utilizing wound-healing and Transwell assays. In addition, protein expressions of COL1A1, COL5A1, E-cadherin, N-cadherin, Snail, and Vimentin were identified via Western blot (WB) assay. Bioinformatics, qRT-PCR, WB, and dual luciferase reporter assays were completed to identify whether miR-29b-3p targeted COL1A1 and COL5A1. In addition, our team explored the treatment effects of miR-29b-3p on a murine heterograft model.ResultsOur findings revealed that miR-29b-3p proved much more regulated downward in PTC tissue specimens than in adjacent non-cancerous tissues. Meanwhile, decreased expression of miR-29b-3p was strongly related to the TNM stage of PTC patients (p<0.001), while overexpression of miR-29b-3p in PTC cells suppressed cellular migration, invasion, proliferation, and EMT. Conversely, silencing miR-29b-3p yielded the opposite effect. COL1A1 and COL5A1 were affirmed as the target of miR-29b-3p. Additionally, the COL1A1 and COL5A1 were highly expressed in PTC tumor samples than in contrast to neighboring healthy samples. Functional assays revealed that overexpression of COL1A1 or COL5A1 reversed the suppressive role of miR-29b-3p in migration, invasion, and EMT of PTC cells. Finally, miR-29b-3p agomir treatment dramatically inhibited Xenograft tumor growth in the animal model.ConclusionsThese findings document that miR-29b-3p inhibited PTC cells invasion and metastasis by targeting COL1A1 and COL5A1; this study also sparks new ideas for risk assessment and miRNA replacement therapy in PTC.