title: MicroRNA-206 attenuates tumor proliferation and migration involving the downregulation of NOTCH3 in colorectal cancer.
abstract: Colorectal cancer (CRC) is the most common cancer diagnosed worldwide, and the development of metastases is a major cause of mortality. Accumulating evidence suggests that microRNAs are important in carcinogenesis by affecting the expression of genes that regulate cancer progression. A number of studies have shown that miR-206 is frequently downregulated in many human malignancies, including CRC, and is associated with a more malignant phenotype. Previous studies involving HeLa and C2C12 cells have validated the inhibitory mechanism of miR-206 via NOTCH3 targeting. However, whether or not the interplay between miR-206 and NOTCH3 also occurs in CRC is unknown. Therefore, we investigated the tumor suppressive and metastatic effects of miR-206 and its target, NOTCH3, in CRC. Based on the inverse association between the expression of miR-206 and NOTCH3 in CRC tissues, miR-206 mimics were transiently transfected into the SW480 (and its metastatic strain) and SW620 colon cancer cell lines. Upregulation of miR-206 inhibited cancer cell prolife-ration and migration, blocked the cell cycle, and activated apoptosis. The tumor suppressive capacity of miR-206 had a similar effect on CRC cells, although with a different metastatic potential, and may be explained by direct NOTCH3 signaling inhibition and indirect cross-talk with other signaling pathways involving CDH2 and MMP-9. These results support miR-206 as a tumor suppressor in CRC and suggest a potential therapeutic target for clinical intervention.
authors.affiliation: Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Huai'an Hospital Affiliated to Xuzhou Medical College, Huai'an, Jiangsu 223002, P.R. China.
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Xi
authors.affiliation: Department of Pathology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Wan
authors.affiliation: Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Hui
authors.affiliation: Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Cao
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014162:Transfection; D014945:Wound Healing / Q000235:genetics
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9