Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-related mortality worldwide. Aberrant expression of miRNAs play important roles in the development and progression of various types of cancers by modulating oncogenic and tumour-suppressor pathways. Therefore, exploring the functions of microRNAs (miRNAs) that specifically contribute to CRC tumourigenesis and tumour development would greatly aid in obtaining more information on CRC and provide new targets for its diagnosis and treatment. miRNA-411 (miR-411) was previously observed to be aberrantly expressed in multiple human cancers. However, the expression pattern, function and underlying molecular mechanism of miR-411 in CRC remain unclear. Therefore, the present study was performed to detect miR-411 expression, investigate the biological roles of miR-411 and identify its mechanism of action in CRC cells. Here, miR-411 expression was significantly downregulated in human CRC tissues and cell lines, and low levels of miR-411 were correlated with lymph node metastasis, distant metastasis and TNM stage. Resumed expression of miR-411 suppressed cell proliferation and invasion but promoted apoptosis in CRC. Additionally, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was identified as a direct target of miR-411 in CRC. PIK3R3 was upregulated in the CRC tissues and inversely correlated with miR-411 expression. Downregulation of PIK3R3 had tumoursuppressive effects similar to those of miR-411 overexpression in CRC. Moreover, upregulation of PIK3R3 could rescue the tumour-suppressing effects of miR-411 overexpression in CRC cells. More importantly, miR-411 specifically suppressed the activation of the AKT/mTOR signalling pathway in CRC. Therefore, miR-411 functions as a tumour-suppressive miRNA by directly targeting PIK3R3 and indirectly regulating AKT/mTOR signalling pathway. miR-411 may serve as a new therapeutic target for patients with CRC.
机构:
Sun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R ChinaSun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R China
Wang, Zengyan
He, Shanyang
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Sun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R ChinaSun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R China
He, Shanyang
Guo, Peng
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Sun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R ChinaSun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R China
Guo, Peng
Guo, Xu
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Sun Yat Sen Univ, Affiliated Hosp 1, Med Examinat Ctr, Guangzhou 510080, Guangdong, Peoples R ChinaSun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R China
Guo, Xu
Zheng, Jingxuan
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Yangjiang Peoples Hosp, Dept Neurol, Yangjiang 529500, Guangdong, Peoples R ChinaSun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R China
机构:
Jilin Univ, Hosp 1, Dept Anesthesiol, Changchun 130021, Jilin, Peoples R ChinaJilin Univ, Hosp 1, Dept Anesthesiol, Changchun 130021, Jilin, Peoples R China
Song, Xuesong
Shi, Bo
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Jilin Univ, Coll Basic Med Sci, Expt Ctr, Changchun 130021, Jilin, Peoples R ChinaJilin Univ, Hosp 1, Dept Anesthesiol, Changchun 130021, Jilin, Peoples R China
Shi, Bo
Huang, Kexin
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Jilin Univ, Coll Basic Med Sci, Expt Ctr, Changchun 130021, Jilin, Peoples R ChinaJilin Univ, Hosp 1, Dept Anesthesiol, Changchun 130021, Jilin, Peoples R China
Huang, Kexin
Zhang, Wenjie
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Jilin Univ, China Japan Union Hosp, Dept Pathol, Changchun 130033, Jilin, Peoples R ChinaJilin Univ, Hosp 1, Dept Anesthesiol, Changchun 130021, Jilin, Peoples R China