Liu JinHui, Li ChunYu, Jiang Yi, Wan YiCong, Zhou ShuLin, Cheng WenJun
1Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 Jiangsu China.
2Emergency Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 China.
Cancer Cell Int. 2018 Apr 2;18:51. doi: 10.1186/s12935-018-0545-8. eCollection 2018.
Endometrial 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.
Expression 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.
We 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.
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.
子宫内膜癌（EC）是全球女性生殖道中第四常见的恶性肿瘤。微小RNA是重要的基因调节因子，在包括肿瘤发生在内的多种生物学过程中发挥关键作用。多项研究表明，miR-139-5p参与了多种癌症的肿瘤发生和转移。然而，其在子宫内膜癌中的表达及潜在生物学作用仍有待确定。本研究旨在探讨miR-139-5p在子宫内膜癌中的表达，并分析其功能及潜在分子机制。
采用qRT-PCR检测miR-139-5p的表达。通过免疫荧光染色检测子宫内膜癌组织及相邻正常组织中HOXA10的表达。使用CCK-8和集落形成试验评估miR-139-5p对ECC1和Ishikawa细胞系增殖的影响。采用Transwell迁移试验研究miR-139-5p对EC细胞迁移的影响。使用荧光素酶报告基因试验和蛋白质免疫印迹法确认miR-139-5p对HOXA10的靶向作用。
我们发现，与配对的相邻非肿瘤组织相比，miR-139-5p在人子宫内膜癌中表达下调。过表达miR-139-5p显著抑制子宫内膜癌细胞的活力和迁移。结合计算算法和双荧光素酶报告基因试验确定HOXA10为miR-139-5p的靶标。miR-139-5p过表达后，子宫内膜癌细胞中HOXA10的表达下调。HOXA10在子宫内膜癌组织中的表达水平显著升高，且与临床子宫内膜癌组织中miR-139-5p的表达呈负相关。
这些发现表明，miR-139-5p靶向HOXA10转录本并抑制子宫内膜癌细胞的生长和迁移，提示miR-139-5p在人类子宫内膜癌发病机制中发挥肿瘤抑制作用。
