AKAP12 endogenous transcripts suppresses the proliferation migration and invasion of colorectal cancer cells by directly targeting oncomiR-183

【作者】 胡婷婷； 李可； 何萍； 关明； 刘维薇；

【机构】 复旦大学附属华山医院； 上海市第十人民医院； 南京医科大学附属南京第一医院；

【摘要】 Objective The causative factors of colorectal cancer are complicated. AKAP12, also known as Gravin/AKAP250 is a tumor suppressor gene and its deregulation may leads to a tumor prone condition. Here we suggested that AKAP12 m RNA might be act as a competitive endogenous regulatory factor to attain its cancer suppression by interacting with onco-microRNAs. Methods mi R-183 was predicted as putative microRNA targeting AKAP12 by bioinformatics analysis, and further confirmed by dual-luciferase reporter assays and quantitative qRT-PCR. The expressions of miR-183 were detected in 21 pairs of CRC stage II tissues and matched noncancerous tissues by quantitative reverse transcription PCR. Gain-and loss-of-function experiments were conducted to investigate the biological functions of miR-183 both in vitro and in vivo. Results Bioinformatics analysis and luciferase assays revealed that AKAP12 mRNA which functioned as a suppressor in regulating CRC metastasis directly controlled the expression of miRNA-183. Mechanistic analysis demonstrated that both in vitro and in vivo anti-miR-183 depressed cell proliferation, migration, and invasion in CRC cells while miR-183 overexpression resulted in the opposite effects. That’s indicated its low expression negatively correlated with CRC tumor progression and metastasis. Conclusions Our findings suggest that oncomiRNA-183 influences the proliferation, migration, invasion of colorectal cancer cells. 3’UTR sites of AKAP12 m RNA may act as a microRNA sponge to capture miRNA-183 to modulate oncogenic properties. This may probably another anti-tumor activity that mediated by the mechanism besides protein. This may provide a new potential treatment of CRC tumors.更多还原

【Abstract】 Objective The causative factors of colorectal cancer are complicated. AKAP12, also known as Gravin/AKAP250 is a tumor suppressor gene and its deregulation may leads to a tumor prone condition. Here we suggested that AKAP12 m RNA might be act as a competitive endogenous regulatory factor to attain its cancer suppression by interacting with onco-microRNAs. Methods miR-183 was predicted as putative microRNA targeting AKAP12 by bioinformatics analysis, and further confirmed by dual-luciferase reporter assays and quantitative qRT-PCR. The expressions of miR-183 were detected in 21 pairs of CRC stage II tissues and matched noncancerous tissues by quantitative reverse transcription PCR. Gain-and loss-of-function experiments were conducted to investigate the biological functions of miR-183 both in vitro and in vivo. Results Bioinformatics analysis and luciferase assays revealed that AKAP12 mRNA which functioned as a suppressor in regulating CRC metastasis directly controlled the expression of miRNA-183. Mechanistic analysis demonstrated that both in vitro and in vivo anti-miR-183 depressed cell proliferation, migration, and invasion in CRC cells while miR-183 overexpression resulted in the opposite effects. That’s indicated its low expression negatively correlated with CRC tumor progression and metastasis. Conclusions Our findings suggest that oncomiRNA-183 influences the proliferation, migration, invasion of colorectal cancer cells. 3’UTR sites of AKAP12 m RNA may act as a microRNA sponge to capture miRNA-183 to modulate oncogenic properties. This may probably another anti-tumor activity that mediated by the mechanism besides protein. This may provide a new potential treatment of CRC tumors.更多还原