MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer

Zhaojing Jiang,Yanfang Zheng,Jiren Zhang,Jing Li,Xiaochun Lin,Rong Zeng,Jingyu Li,Qiancheng Song,Xing Chen

doi:10.18632/oncotarget.9850

Zhaojing Jiang, Yanfang Zheng + Show 7 more

Open Access

https://doi.org/10.18632/oncotarget.9850

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Abstract

Repeated infection with high-risk HPV is a major cause for the development and metastasis of human cervical cancer, even though the mechanism of the metastasis is still not completely understood. Here, we reported that miR-218 (microRNA-218) was downregulated in cervical cancer tissues, especially in metastatic cancer tissues. We found that miR-218 expression was associated with clinicopathological characteristics of patients with cervical cancer. MiR-218 overexpression inhibited Epithelial-Mesenchymal Transition (EMT), migration and invasiveness of cervical cancer cells in vitro. Moreover, miR-218 repressed the expression of SFMFBT1 (Scm-like with four MBT domains 1) and DCUN1D1 (defective in cullin neddylation 1, domain containing 1) by direct binding to the 3′UTRs of the mRNAs. The overexpression of SFMBT1 induced EMT and increased the migration and invasiveness of cervical cancer cells, while the overexpression of DCUN1D1 increased the migration and invasiveness of these cells, but did not induce EMT. An inverse correlation was observed between the expression of miR-218 and DCUN1D1 protein in cervical cancer tissues. Importantly, HPV16 E6 downregulated the expression of miR-218 in cervical cancer, while miR-218 rescued the promotion effect of HPV16 E6 on the expression of SFMBT1 and DCUN1D1. Taken together, our results revealed that HPV16 E6 promoted EMT and invasion in cervical cancer via the repression of miR-218, while miR-218 inhibited EMT and invasion in cervical cancer by targeting SFMBT1 and DCUN1D1.

Highlights

Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in females worldwide [1]
In order to identify the role of miR-218 in cervical cancer, we detected the expression of miR-218 in a cervical cancer tissue microarray that contained 94 cervical cancer tissues and 10 adjacent normal cervical tissues (Table 1)
The results showed that knockdown of SFMBT1 or DCUN1D1 inhibited invasion of cervical cancer cell as those that were observed in miR-218 overexpression treatment (Figure 5A and 5B)

Summary

Introduction

Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in females worldwide [1]. The prognosis of patients with cervical cancer remains unsatisfactory, especially for those with advanced-stage tumors. Tumor metastases are responsible for approximately 90% of all cancer-related deaths [2]. The identification of causes and potential markers of metastasis are important in order to promote an early diagnosis, predict the prognosis and develop novel therapeutic strategies for cervical cancer. Recent studies have indicated that miRNAs are aberrantly expressed in different types of tumor tissues at various developmental stages and are considered to be master regulators of many important biological processes, including cell proliferation, apoptosis, and the stress response [4, 5]. Studies have documented the role of miRNAs in metastasis, cellular migration, invasion, and EMT [6,7,8]. Compelling evidence shows that a number of miRNAs including miR-424, miR-29a, miR-375, www.impactjournals.com/oncotarget participate in the invasion and metastasis of cervical cancer [9, 10]

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