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

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...

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Detalles Bibliográficos
Autores principales: Zhou, Mingyue, Bian, Zehua, Liu, Bingxin, Zhang, Yi, Cao, Yulin, Cui, Kaisa, Sun, Shengbai, Li, Jiuming, Zhang, Jia, Wang, Xue, Li, Chaoqun, Yao, Surui, Yin, Yuan, Fei, Bojian, Huang, Zhaohui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982620/
https://www.ncbi.nlm.nih.gov/pubmed/33686713
http://dx.doi.org/10.1002/cam4.3830
Descripción
Sumario: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.