MicroRNA‑219a‑2‑3p modulates the proliferation of thyroid cancer cells via the HPSE/cyclin D1 pathway

Yang,Chuanjia; Zhang,Siyang; Chang,Xiaoying; Huang,Yonglian; Cui,Dongxu; Liu,Zhen

doi:10.3892/etm.2021.10091

MicroRNA‑219a‑2‑3p modulates the proliferation of thyroid cancer cells via the HPSE/cyclin D1 pathway

Authors:
- Chuanjia Yang
- Siyang Zhang
- Xiaoying Chang
- Yonglian Huang
- Dongxu Cui
- Zhen Liu
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Affiliations: Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Science and Experiment Center, China Medical University, Shenyang, Liaoning 110122, P.R. China, Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: April 20, 2021 https://doi.org/10.3892/etm.2021.10091
Article Number: 659

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Abstract

Heparanase (HPSE) is an endo‑β‑D‑glucuronidase overexpressed in different types of human cancer, and a predicted target of microRNA (miRNA/miR)‑219a‑2‑3p in thyroid cancer. The present study aimed to investigate the potential role of HPSE and miR‑219a‑2‑3p in thyroid cancer, and the molecular mechanism of miR‑219a‑2‑3p regulating the proliferation of thyroid cancer cells via HPSE was confirmed. Immunohistochemistry analysis was performed to detect HPSE expression in thyroid cancer sections. In addition, reverse transcription‑quantitative PCR analysis was performed to detect mRNA and miR‑219a‑2‑3p expression levels in thyroid cancer samples and cell lines. miR‑219‑2‑3p mimic or HPSE plasmid were transfected into B‑CPAP and TPC‑1 thyroid cancer cells. Furthermore, western blot analysis was performed to detect the protein expression levels of HPSE and cyclin D1. Cell cycle analysis was performed using propidium iodide staining and flow cytometry, and EdU incorporation was performed to detect cell proliferation. The results demonstrated that high HPSE expression was significantly associated with tumor size, extracapsular invasion and lymph node metastasis. Notably, a statistically negative correlation was observed between HPSE mRNA expression and miR‑219a‑2‑3p expression in thyroid cancer tumors, as well as in thyroid cancer cell lines. When exogenously expressed in B‑CPAP and TPC‑1 cells, miR‑219a‑2‑3p induced cell cycle arrest at the G0/G1 phase and decreased the percentage of proliferating cells. Furthermore, HPSE and cyclin D1 protein expression decreased following transfection with miR‑219a‑2‑3p. Notably, when HPSE was ectopically expressed in miR‑219a‑2‑3p transfected cells, cyclin D1 expression and the number of proliferative cells increased. Taken together, these results suggest that HPSE contributes to the proliferation of thyroid cancer cells. In addition, miR‑219a‑2‑3p was confirmed to target HPSE and inhibit cell proliferation, which was associated with cyclin D1 suppression‑mediated cell cycle arrest.

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