Mechanism of lnc-AC079612.1.1-1∶1 in hepatic metastasis of colon cancer
10.3760/cma.j.issn.1673-4203.2018.08.006
- VernacularTitle:lnc-AC079612.1.1-1∶1参与结肠癌肝转移的机制研究
- Author:
Wei ZHANG
1
;
Bo WANG
;
Zhanlong SHEN
;
Kewei JIANG
;
Yingjiang YE
;
Shan WANG
;
Kai SHEN
Author Information
1. 100044,北京大学人民医院胃肠外科外科肿瘤研究室结直肠癌诊疗研究北京市重点实验室
- Keywords:
Colonic neoplasms;
Micro RNAs;
Neoplasm invasiveness;
Liver metastasis;
IncRNA
- From:
International Journal of Surgery
2018;45(8):523-528,封4
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of lnc-AC079612.1-1∶1 in the metastasis of colorectal cancer by regulating miR-1915 expression and provide a theoretical basis for new therapeutic targets of colon cancer.Methods Continuously harvested 3 pairs of primary tumor and hepatic metastases of patients with synchronous colon cancer with liver metastasis.LncRNA + mRNA Human Gene Expression Microarray V4.0 and 4 × 180K Expression Microarray were used to detect the Expression profile of LncRNA in primary colon cancer and matched liver metastases.The detection of expression profile chip was used to find some lncRNAs that may be closely associated with colon cancer liver metastasis,and through the literature retrieval,the author preliminarily analyzed the co-expression encoding genes of lncRNAs,in order to find lncRNAs that may play key roles in the process of colon cancer liver metastasis.The effect of lnc-AC079612.1.1-1∶1 on the proliferation capacity of colon cancer cell lines was detected in SW480 cell lines and SW620 cell lines of colon cancer through CCK-8 experiment.Effects of lnc-AC079612.1.1-1∶1 on the migration and invasion of colon cancer cells were examined by Transwell cell invasion assay.Through TargetScan,Miranda,LNCipedia and other web tools,miRNAs that may bind to lncRNA and o-6-methylguanine-DNA methyl transferase (MGMT) were predicted.Double luciferase reporter gene assay was used to detect the interaction between miR-1915 andlnc-AC079612.1.1-1 ∶ 1.SPSS 22.0 statistical software was used to analyze the data.The measurement data were expressed as ((x) ± s).T test was compared between the two groups,and multiple groups were compared with F test.Results The expression of lnc-AC079612.1-1 ∶ 1 was 3.94 times higher in the liver metastases than in the primary tumor,and expression of MGMT was 3.74 times higher in the liver metastases than in the primary tumor.The results showed that there was a significant co-expression relationship between the lncRNA and o-6-methylguanine DNA transferase (MGMT) gene,and the co-expression correlation coefficient was 0.994 (P ＜ 0.001).The over expression of lnc-ac079612.1.1-1∶1 could significantly enhance the proliferation capacity of SW480 and SW620 cell lines of colon cancer through the CCK-8 experiment.The over expression of lnc-ac079612.1.1-1:1 could promote the invasion and metastasis of SW480 and SW620 cell lines of colon cancer through Transwell cell invasion experiment.MirR-1915-3p was the only miRNA that predicted to be combined with lnc-ac079612.1-1∶1 and MGMT through TargetScan,Miranda,LNCipedia and other web tools.Lnc-ac079612.1.1-1∶1 was found to bind to miR-1915 by double luciferase assay.Conclusion Lnc-ac079612.1.1-1∶ 1 may participate in the liver metastasis process of colon cancer by regulating MGMT,and may play a role in the liver metastasis of colon cancer through the action of mir-1915 on MGMT.
