Tumor-suppressor role of miR-139-5p in endometrial cancer

Jinhui Liu,Yi Jiang,Wenjun Cheng,Shulin Zhou,Chunyu Li,Yicong Wan

doi:10.1186/s12935-018-0545-8

Jinhui Liu, Yi Jiang + Show 4 more

Open Access

https://doi.org/10.1186/s12935-018-0545-8

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Abstract

BackgroundEndometrial cancer (EC) is the fourth most common malignancy of the female genital tract worldwide. MicroRNAs are important gene regulators with critical roles in diverse biological processes, including tumorigenesis. Several study’s show that miR-139-5p is involved in the tumorigenesis and metastasis of various cancers. However, its expression and potential biologic role in endometrial cancer remain to be determined. This study aimed to investigate the miR-139-5p expression and to analyze its function and underlying molecular mechanism in endometrial cancer.MethodsExpression of miR-139-5p was measured using qRT-PCR. The expression of HOXA10 was detected by Immunofluorescence staining in endometrial cancer tissues and adjacent normal tissues. CCK-8 and colony formation assays were used to assess the effect of miR-139-5p on ECC1 and Ishikawa cell line proliferation. Transwell migration assay was used to study the effect of miR-139-5p on EC cell migration. Luciferase reporter assay and western blot were used to confirm targeting of HOXA10 by miR-139-5p.ResultWe demonstrated that miR-139-5p was down-regulated in human endometrial cancer compared to their matched adjacent non-tumor tissues. Overexpressed miR-139-5p significantly inhibited endometrial cancer cell viability and migration. Computational algorithm in combination with dual luciferase reporter assays identified HOXA10 as the target of miR-139-5p. HOXA10 expression was downregulated in endometrial cancer cells after miR-139-5p overexpression. The expression level of HOXA10 was significantly increased in endometrial cancer tissues, which was inversely correlated with miR-139-5p expression in clinical endometrial cancer tissues.ConclusionThese findings indicate that miR-139-5p targets the HOXA10 transcript and suppresses endometrial cancer cell growth and migration, suggesting that miR-139-5p acts as a tumor suppressive role in human endometrial cancer pathogenesis.

Highlights

Endometrial cancer (EC) is the fourth most common malignancy of the female genital tract worldwide
These findings indicate that miR-139-5p targets the HOXA10 transcript and suppresses endometrial cancer cell growth and migration, suggesting that miR-139-5p acts as a tumor suppressive role in human endometrial cancer pathogenesis
Downregulation of miR‐139‐5p expression occurs in EC tissues To determine the role of miR-139-5p in endometrial cancer development, we examined the expression of miR139-5p in twenty-five endometrial cancer samples and fifteen adjacent normal tissues by RT-polymerase chain reaction (PCR)

Summary

Introduction

Endometrial cancer (EC) is the fourth most common malignancy of the female genital tract worldwide. Many evidences have shown that miRNAs are involved in many cellular processes, including development, apoptosis, differentiation, metabolism and stress response, depending upon the regulation of specific target genes [6]. MiR-10b inhibits apoptosis and promotes proliferation and invasion of EC cells via targeting HOXB3 [7]. Many miRNAs are closely associated with malignancy, including facts such as tumor progression, potential prognostic markers and chemotherapy resistance in endometrial cancers [5, 12, 13]. In the tumor-associated miRNAs, the mechanism of miR-139-5p in cancer initiation and progression drew our attention, because miR-139-5p has been found to perform various biological functions in other types of malignancy, such as bladder, colon, esophageal, liver and lung cancer [14,15,16,17]. There has not been any thorough research investigating the association between miR-139-5p and EC

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