Shuang Zheng1, Feng Lin1, Meng Zhang1, Junhui Fu1, Xiaogang Ge1, Ning Mu1. 1. Department of General Surgery, Huangyan Hospital of Wenzhou Medical University, Taizhou First People's Hospital Taizhou 318020, Zhejiang Province, China.
Abstract
BACKGROUND: Long noncoding RNA (LncRNA) functions as multiple mechanisms, including DNA methylation in colorectal cancer (CRC). ADAMTS12 was applied as biomarkers in CRC via abnormally DNA methylation. Lnc-AK001058 gene, which was reported dysregulated in CRC, is located adjacent to the gene ADAMTS12. However, little is known about the role of AK001058 during the proliferation and migration of CRC. MATERIAL AND METHODS: In present study, quantitative RT-PCR were used to measure AK001058 and ADAMTS12 expression levels, and western blotting assays were performed to measure ADAMTS12 expression in CRC cells. Methylation-specific PCR (MSP) was applied to measure the methylation of the CpG islands of the ADAMTS12 promoter. Cell proliferation, migration, invasion and cycle assays ware utilized to analyze the role of AK001058 in CRC. RESULTS: The results indicated that the expression of AK001058 was significantly increased in CRC. Overexpression of AK001058 could suppress the expression of ADAMTS12. AK001058 also significantly promoted cell proliferation, migration and invasion, and prolonged S stage of CRC, while silencing the expression of AK001058 showed contrary effects. Moreover, compared with negative control and AK001058-NC groups, overexpression of AK001058 could increase the DNA methylation level of ADAMTS12 gene promoter in CRC, while si-AK001058 could reverse this effect. CONCLUSION: In conclusion, AK001058 promotes the proliferation, invasion, migration, and prolonged S stage of CRC by regulating methylation of ADAMTS12. Our research will provide new insights for the biomarker of colorectal cancer diagnose and new clues for clinical treatment. AJTR
BACKGROUND: Long noncoding RNA (LncRNA) functions as multiple mechanisms, including DNA methylation in colorectal cancer (CRC). ADAMTS12 was applied as biomarkers in CRC via abnormally DNA methylation. Lnc-AK001058 gene, which was reported dysregulated in CRC, is located adjacent to the gene ADAMTS12. However, little is known about the role of AK001058 during the proliferation and migration of CRC. MATERIAL AND METHODS: In present study, quantitative RT-PCR were used to measure AK001058 and ADAMTS12 expression levels, and western blotting assays were performed to measure ADAMTS12 expression in CRC cells. Methylation-specific PCR (MSP) was applied to measure the methylation of the CpG islands of the ADAMTS12 promoter. Cell proliferation, migration, invasion and cycle assays ware utilized to analyze the role of AK001058 in CRC. RESULTS: The results indicated that the expression of AK001058 was significantly increased in CRC. Overexpression of AK001058 could suppress the expression of ADAMTS12. AK001058 also significantly promoted cell proliferation, migration and invasion, and prolonged S stage of CRC, while silencing the expression of AK001058 showed contrary effects. Moreover, compared with negative control and AK001058-NC groups, overexpression of AK001058 could increase the DNA methylation level of ADAMTS12 gene promoter in CRC, while si-AK001058 could reverse this effect. CONCLUSION: In conclusion, AK001058 promotes the proliferation, invasion, migration, and prolonged S stage of CRC by regulating methylation of ADAMTS12. Our research will provide new insights for the biomarker of colorectal cancer diagnose and new clues for clinical treatment. AJTR
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