Department of Colorectal Cancer, Shanxi Cancer Hospital and Institute, The Third People's Hospital of Shanxi Province, No. 3 Xinchun Road, Taiyuan, 030013, China.
Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, 030013, China.
Clin Transl Oncol. 2018 Jun;20(6):703-712. doi: 10.1007/s12094-017-1770-7. Epub 2017 Oct 25.
The expression of miR-489 is linked to tumor development and progression; nevertheless, its role in tumor growth and invasion of colorectal cancer (CRC) and the underlying mechanism has not been clarified.
We used quantitative RT-PCR to measure the expression of mature miR-489 in human colorectal tissues and the corresponding CRCs. Targets of miR-489 were predicted with TargetScan and substantiated by dual-luciferase reporter assay. Furthermore, we did in vitro and in vivo analysis with expression vectors and small interfering RNAs, to elucidate the precise role of miR-489 and its target gene histone deacetylase 7 (HDAC7) on cell proliferation, survival, and invasion.
Compared to the corresponding non-tumor tissues, miR-489 was frequently downregulated in CRC. By Kaplan-Meier analysis, we found that lower CRC recurrence free survival years in the group with elevated miR-489 expression than those with lower miR-489 expression. In addition, we examined that miR-489 obviously inhibited the migratory and invasive capability in CRC. In further study, we found that miR-489 targets the 3'-UTR of the HDAC7 transcript and downregulates its expression, and HDAC7 expression promoted tumor cell proliferation and invasion. We demonstrated that miR-489 suppresses tumor invasion and metastasis in CRC by targeting HDAC7.
We identified that MiR-489 suppresses tumor growth and invasion in CRC by targeting HDAC7. The expression of miR-489 suggests CRC recurrence and metastasis, which shed crucial light on how miR-489 functions in CRC pathogenesis.
miR-489 的表达与肿瘤的发生和发展有关；然而，其在结直肠癌（CRC）肿瘤生长和侵袭中的作用及其潜在机制尚不清楚。
我们使用定量 RT-PCR 测量了人结直肠组织和相应 CRC 中成熟 miR-489 的表达。使用 TargetScan 预测 miR-489 的靶标，并通过双荧光素酶报告基因实验进行验证。此外，我们通过表达载体和小干扰 RNA 进行了体外和体内分析，以阐明 miR-489 及其靶基因组蛋白去乙酰化酶 7（HDAC7）在细胞增殖、存活和侵袭中的精确作用。
与相应的非肿瘤组织相比，CRC 中 miR-489 常下调。通过 Kaplan-Meier 分析，我们发现 miR-489 表达升高的 CRC 患者的无复发生存年限低于 miR-489 表达较低的患者。此外，我们发现 miR-489 明显抑制 CRC 的迁移和侵袭能力。在进一步的研究中，我们发现 miR-489 靶向 HDAC7 转录本的 3'-UTR 并下调其表达，HDAC7 表达促进肿瘤细胞增殖和侵袭。我们证明 miR-489 通过靶向 HDAC7 抑制 CRC 中的肿瘤侵袭和转移。
我们确定 miR-489 通过靶向 HDAC7 抑制 CRC 中的肿瘤生长和侵袭。miR-489 的表达提示 CRC 复发和转移，这为 miR-489 在 CRC 发病机制中的作用提供了重要线索。
