PMID- 33686713 OWN - NLM STAT- MEDLINE DCOM- 20210719 LR - 20210719 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 10 IP - 7 DP - 2021 Apr TI - Long noncoding RNA MCM3AP-AS1 enhances cell proliferation and metastasis in colorectal cancer by regulating miR-193a-5p/SENP1. PG - 2470-2481 LID - 10.1002/cam4.3830 [doi] AB - 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. CI - (c) 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Zhou, Mingyue AU - Zhou M AD - Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Bian, Zehua AU - Bian Z AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Liu, Bingxin AU - Liu B AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Zhang, Yi AU - Zhang Y AD - Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. FAU - Cao, Yulin AU - Cao Y AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Cui, Kaisa AU - Cui K AUID- ORCID: 0000-0001-7255-2689 AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Sun, Shengbai AU - Sun S AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Li, Jiuming AU - Li J AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Zhang, Jia AU - Zhang J AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Wang, Xue AU - Wang X AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Li, Chaoqun AU - Li C AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Yao, Surui AU - Yao S AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Yin, Yuan AU - Yin Y AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. FAU - Fei, Bojian AU - Fei B AD - Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. FAU - Huang, Zhaohui AU - Huang Z AUID- ORCID: 0000-0002-0117-9976 AD - Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. AD - Cancer Epigenetics Program, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210308 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (MIRN193 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Antisense) RN - 0 (RNA, Long Noncoding) RN - EC 2.3.1.- (Acetyltransferases) RN - EC 2.3.1.- (MCM3AP protein, human) RN - EC 3.4.- (SENP1 protein, human) RN - EC 3.4.22.- (Cysteine Endopeptidases) SB - IM MH - Acetyltransferases/genetics/*metabolism MH - Animals MH - Cell Proliferation/genetics MH - Colorectal Neoplasms/genetics/*metabolism/mortality/pathology MH - Cysteine Endopeptidases/*metabolism MH - Gene Silencing MH - Humans MH - Intracellular Signaling Peptides and Proteins/genetics/*metabolism MH - Lung Neoplasms/secondary MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - MicroRNAs/*metabolism MH - Neoplasm Invasiveness MH - Neoplasm Metastasis/genetics MH - Neoplasm Transplantation MH - Prognosis MH - RNA, Antisense/metabolism MH - RNA, Long Noncoding/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Stem Cell Assay MH - Up-Regulation PMC - PMC7982620 OTO - NOTNLM OT - MCM3AP antisense RNA 1 OT - SENP1 OT - colorectal cancer OT - long noncoding RNAs OT - microRNAs COIS- The authors declare that they have no conflict of interest. EDAT- 2021/03/10 06:00 MHDA- 2021/07/20 06:00 PMCR- 2021/03/08 CRDT- 2021/03/09 06:17 PHST- 2021/02/01 00:00 [revised] PHST- 2020/11/08 00:00 [received] PHST- 2021/02/05 00:00 [accepted] PHST- 2021/03/10 06:00 [pubmed] PHST- 2021/07/20 06:00 [medline] PHST- 2021/03/09 06:17 [entrez] PHST- 2021/03/08 00:00 [pmc-release] AID - CAM43830 [pii] AID - 10.1002/cam4.3830 [doi] PST - ppublish SO - Cancer Med. 2021 Apr;10(7):2470-2481. doi: 10.1002/cam4.3830. Epub 2021 Mar 8.