长链非编码 RNA MCM3AP-AS1 通过调节 miR-193a-5p/SENP1 促进结直肠癌细胞增殖和转移。
Long noncoding RNA MCM3AP-AS1 enhances cell proliferation and metastasis in colorectal cancer by regulating miR-193a-5p/SENP1.
机构信息
Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
出版信息
Cancer Med. 2021 Apr;10(7):2470-2481. doi: 10.1002/cam4.3830. Epub 2021 Mar 8.
BACKGROUND
Accumulating evidences have shown that long noncoding RNAs (lncRNAs) play key roles in many diseases, including cancer. Several studies reported that MCM3AP antisense RNA 1 (MCM3AP-AS1) was associated with the tumorigenesis and progression. However, the specific function and mechanism of MCM3AP-AS1 in colorectal cancer (CRC) have not been fully understood.
METHODS
The expression of MCM3AP-AS1 was detected by quantitative reverse transcription PCR (RT-qPCR) in CRC tissues and matched noncancerous tissues (NCTs). CCK-8 assay, colony formation assay, transwell assay, xenograft and lung metastasis mouse models were used to examine the tumor-promoting function of MCM3AP-AS1 in vitro and in vivo. The binding relationship between MCM3AP-AS1, miR-193a-5p and sentrin-specific peptidase 1 (SENP1) were screened and identified by databases, RT-qPCR, dual luciferase reporter assay and western blot.
RESULTS
In the present study, we got that the expression of MCM3AP-AS1 was higher in CRC tissues than in paired NCTs, and increased MCM3AP-AS1 expression was associated with adverse outcomes in CRC patients. Functional experiments in vitro revealed that silencing of MCM3AP-AS1 could inhibit the proliferation, colony formation, migratory, and invasive abilities of CRC cells. The mouse models of xenograft and lung metastasis further confirmed that in vivo silencing MCM3AP-AS1 could significantly inhibit the growth and metastasis of CRC. Further mechanism studies indicated that MCM3AP-AS1 could sponge miR-193a-5p and inhibit the activity of it. What is more, SENP1 was proved to be a novel target of miR-193a-5p and could be upregulated by MCM3AP-AS1. At last, we observed that SENP1 overexpression in CRC tissues was closely related to unfavorable prognosis.
CONCLUSION
Taken together, we identified in CRC the MCM3AP-AS1/miR-193a-5p/SENP1 regulatory axis, which affords a therapeutic possibility for CRC.
背景
越来越多的证据表明，长链非编码 RNA（lncRNA）在包括癌症在内的许多疾病中发挥着关键作用。有几项研究报道，MCM3AP 反义 RNA 1（MCM3AP-AS1）与肿瘤的发生和发展有关。然而，MCM3AP-AS1 在结直肠癌（CRC）中的具体功能和机制尚未完全阐明。
方法
采用实时定量逆转录 PCR（RT-qPCR）检测 CRC 组织及配对癌旁组织（NCT）中 MCM3AP-AS1 的表达。CCK-8 检测、集落形成检测、Transwell 检测、异种移植和肺转移小鼠模型用于体外和体内研究 MCM3AP-AS1 的促肿瘤作用。通过数据库、RT-qPCR、双荧光素酶报告基因检测和 Western blot 筛选和鉴定 MCM3AP-AS1、miR-193a-5p 和 SENP1 之间的结合关系。
结果
本研究发现，MCM3AP-AS1 在 CRC 组织中的表达高于配对的 NCTs，并且 MCM3AP-AS1 表达增加与 CRC 患者的不良预后相关。体外功能实验表明，沉默 MCM3AP-AS1 可抑制 CRC 细胞的增殖、集落形成、迁移和侵袭能力。异种移植和肺转移小鼠模型进一步证实，体内沉默 MCM3AP-AS1 可显著抑制 CRC 的生长和转移。进一步的机制研究表明，MCM3AP-AS1 可海绵吸附 miR-193a-5p 并抑制其活性。更重要的是，SENP1 被证明是 miR-193a-5p 的一个新靶点，可被 MCM3AP-AS1 上调。最后，我们观察到 CRC 组织中 SENP1 的过表达与不良预后密切相关。
结论
综上所述，我们在 CRC 中鉴定了 MCM3AP-AS1/miR-193a-5p/SENP1 调控轴，为 CRC 的治疗提供了一种可能。
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