MiR-4454 up-regulated by HPV16 E6/E7 promotes invasion and migration by targeting ABHD2/NUDT21 in cervical cancer.

Hui Wang,Hui Hu,Man Zhu,Zhongxin Lu,Zhenzhao Luo,Jing Wang,Wangze Wu,Shuiyi Liu,Yingle Liu

doi:10.1042/bsr20200796

Abstract

The abnormal expression of HPV16 E6/E7 activates oncogenes and/or inactivates tumor suppressor genes, resulting in the selective growth and malignant transformation of cancer cells. miR-4454 was selected by sequencing due to its abnormal high expression in HPV16 E6/E7 positive CaSki cell compared with HPV16 E6/E7 negative C33A cell. Overexpression of miR-4454 enhances cervical cancer cell invasion and migration. ABHD2 and NUDT21 are identified as a target gene of miR-4454.The effects of ABHD2 and NUDT21 on migration and invasion of CaSki and C33A cells were determined. The dual luciferase and RT-qPCR assays confirmed that miR-4454 might regulate its targets ABHD2 and NUDT21 to promote the proliferation, invasion and migration, whereas, inhibit the apoptosis in CaSki and C33A cells.

Highlights

The incidence of cervical cancer ranks the second among all female tumors with nearly 500,000 women worldwide diagnosed with cervical cancer every year, nearly half of whom die of the disease [1,2]
The results showed that the HPV16 E6/E7 positive cell CaSki expressed higher levels of miR-4454 than HPV16 E6/E7 negative cell C33A
MiR-4454 mimics significantly increased the proliferation of CaSki cells, there was no significant difference in the effect between CaSki and C33A cells

Summary

Introduction

The incidence of cervical cancer ranks the second among all female tumors with nearly 500,000 women worldwide diagnosed with cervical cancer every year, nearly half of whom die of the disease [1,2]. It has been confirmed that cervical cancer is associated with high-risk human papillomavirus (HPV) infection, with HPV16 and HPV18 being the most common infectious agents found in 99.7% of cases of cervical squamous cell carcinoma and 94–100% of cases of cervical adenocarcinoma [1,3,4,5,6]. In HPV-positive cervical cancers, all of the malignant cells contain at least one copy of the viral genome with transcriptional activity [7,8]. We investigated the molecular mechanism of HPV16 E6/E7-regulating miRNA in cervical cancer progress. We used HPV16 E6/E7-positive human cervical cancer cell line CaSki as the major cell model. The aim of the present study was to elucidate the biological functions and potential target of miR-4454 in cervical cancer cells and provide evidence that miR-4454 may serve a potential candidate for the clinical treatment for cervical cancer

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