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miR-372-3p 通过靶向 LATS2 促进结直肠癌的肿瘤进展。

MiR-372-3p promotes tumor progression by targeting LATS2 in colorectal cancer.

机构信息

Department of Anorectal Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8332-8344. doi: 10.26355/eurrev_201910_19144.

Abstract

OBJECTIVE

Many studies suggest that microRNAs can promote the malignant development of tumors. MiRNA-372-3p (miR-372-3p) has been proved to be associated with a variety of cancers. However, the role of miR-372-3p in colorectal cancer (CRC) is unclear.

PATIENTS AND METHODS

We analyzed the expression of miR-372-3p in CRC tissues and several CRC cell lines by quantitative Real Time-PCR. The relationship between miR-372-3p and clinical pathology was also analyzed in CRC patients. Kaplan-Meier analysis and Cox multivariate analysis were used to evaluate the prognostic significance of miR-372-3p in CRC. Next, we investigated the biological function of miR-372-3p, including cell proliferation, migration, and invasion and analyzed its potential molecular mechanism in vivo and in vitro.

RESULTS

Our data showed that the expression of miR-372-3p was dramatically increased in CRC tissues compared with normal tissues. Moreover, the high expression of miR-372-3p was significantly correlated with tumor size and differentiation. Kaplan-Meier analysis showed that the high miR-372-3p expression group patients had a significantly shorter recurrence-free survival (RFS) and disease-specific survival (DSS) than those with the low miR-372-3p group. The analysis of the prognostic factors revealed that miR-372-3p was an independent prognostic factor for RFS and DSS in CRC patients. The knockdown of miR-372-3p inhibited the proliferation, migration, and invasion in HCT116 and SW480 cells. Interestingly, the overexpression of LATS2 partially reversed the miR-372-3p -mediated cell proliferation, migration, and invasion of CRC. Besides, the Hippo signaling pathway was demonstrated to be activated by decreasing of miR-372-3p in CRC. Thus, our study revealed that miR-372-3p is involved in CRC progression by inhibiting the Hippo signaling pathway through its target LATS2. MiR-372-3p and its target genes with signaling pathways are new hope for precise treatment of CRC.

CONCLUSIONS

The upregulation of miR-372-3p was involved in the process of CRC progression by inhibiting the Hippo signaling pathway through inhibition of LATS2. We showed that miR-372-3p and its target genes with signaling pathways are a novel hope for precise treatment of CRC.

摘要

目的

许多研究表明 microRNAs 可以促进肿瘤的恶性发展。miRNA-372-3p(miR-372-3p)已被证明与多种癌症有关。然而,miR-372-3p 在结直肠癌(CRC)中的作用尚不清楚。

患者和方法

我们通过定量实时 PCR 分析了 CRC 组织和几种 CRC 细胞系中 miR-372-3p 的表达。还分析了 miR-372-3p 与 CRC 患者临床病理的关系。Kaplan-Meier 分析和 Cox 多因素分析用于评估 miR-372-3p 在 CRC 中的预后意义。接下来,我们研究了 miR-372-3p 的生物学功能,包括细胞增殖、迁移和侵袭,并在体内和体外分析了其潜在的分子机制。

结果

我们的数据显示,与正常组织相比,CRC 组织中 miR-372-3p 的表达明显增加。此外,miR-372-3p 的高表达与肿瘤大小和分化显著相关。Kaplan-Meier 分析表明,miR-372-3p 高表达组患者的无复发生存(RFS)和疾病特异性生存(DSS)明显短于 miR-372-3p 低表达组。预后因素分析表明,miR-372-3p 是 CRC 患者 RFS 和 DSS 的独立预后因素。抑制 miR-372-3p 可抑制 HCT116 和 SW480 细胞的增殖、迁移和侵袭。有趣的是,LATS2 的过表达部分逆转了 miR-372-3p 介导的 CRC 细胞增殖、迁移和侵袭。此外,在 CRC 中,Hippo 信号通路被证明通过降低 miR-372-3p 而被激活。因此,我们的研究表明,miR-372-3p 通过抑制其靶基因 LATS2 抑制 Hippo 信号通路参与 CRC 进展。miR-372-3p 及其具有信号通路的靶基因是 CRC 精确治疗的新希望。

结论

miR-372-3p 通过抑制靶基因 LATS2 抑制 Hippo 信号通路,参与 CRC 进展过程。我们表明,miR-372-3p 及其具有信号通路的靶基因是 CRC 精确治疗的新希望。

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