1. Academic Validation
  2. Long noncoding RNA MCM3AP-AS1 enhances cell proliferation and metastasis in colorectal cancer by regulating miR-193a-5p/SENP1

Long noncoding RNA MCM3AP-AS1 enhances cell proliferation and metastasis in colorectal cancer by regulating miR-193a-5p/SENP1

  • Cancer Med. 2021 Apr;10(7):2470-2481. doi: 10.1002/cam4.3830.
Mingyue Zhou 1 2 3 Zehua Bian 2 3 Bingxin Liu 2 3 Yi Zhang 4 Yulin Cao 2 3 Kaisa Cui 2 3 Shengbai Sun 2 3 Jiuming Li 2 3 Jia Zhang 2 3 Xue Wang 3 Chaoqun Li 2 3 Surui Yao 2 3 Yuan Yin 2 3 Bojian Fei 1 Zhaohui Huang 2 3
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
  • 2 Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
  • 3 Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
  • 4 Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Abstract

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.

Keywords

MCM3AP antisense RNA 1; SENP1; colorectal cancer; long noncoding RNAs; microRNAs.

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