Mingyue Zhou1,2,3, Zehua Bian2,3, Bingxin Liu2,3, Yi Zhang4, Yulin Cao2,3, Kaisa Cui2,3, Shengbai Sun2,3, Jiuming Li2,3, Jia Zhang2,3, Xue Wang3, Chaoqun Li2,3, Surui Yao2,3, Yuan Yin2,3, Bojian Fei1, Zhaohui Huang2,3. 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.
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.
Authors: Soudeh Ghafouri-Fard; Tayyebeh Khoshbakht; Bashdar Mahmud Hussen; Mohammad Taheri; Mohammad Samadian Journal: Cancer Cell Int Date: 2022-07-05 Impact factor: 6.429