title: Transforming growth factor (TGF) β1 acted through miR-130b to increase integrin α5 to promote migration of colorectal cancer cells.
abstract: Transforming growth factor (TGF)-β1 is a significant stimulator of tumor invasion and metastasis. More recently, it has been found that TGF-β1 acts through microRNAs to regulate their target genes to promote cancer progresses. However, such similar regulation is rarely reported in colorectal cancer (CRC). Here, we observed a decrease in TGF-β1 expression in CRC specimens, compared with matched adjacent normal tissues. In parallel, there was an increase in miR-130b characterized in the same samples by microarray assay. Further, treatment of CRC cells with TGF-β1 caused a significant decrease in the expression of miR-130b and an increased CRC cell migration. Luciferase reporter assay revealed that miR-130b directly targeted the 3' untranslated region (3'UTR) region of integrin α5 gene, which encodes a key molecule involved in cell motility. Subsequently, in the overexpression of miR-130b CRC cells, we observed a decreased level of integrin α5 protein. The regulation of integrin α5 by miR-130b was further shown using the miR-130b mimics and inhibitor of miR-130b. And, knockdown miR-130b with inhibitor in the overexpression of miR-130b CRC cells recovered integrin α5 expression and integrin α5-mediated cell motility. Moreover, the inverse relevance between miR-130b and integrin α5 was also observed in CRC specimens. At last, the enhancement of integrin α5 in TGF-β1-treated cells can be reversed partly when rescuing miR-130b expression. Together, our findings suggested that TGF-β1 acted through miR-130b to promote integrin α5 expression, resulting in the enhanced migration of CRC cells.
authors.affiliation: Peking University Fifth School of Clinical Medicine, Beijing Hospital, Beijing, 100730, China.|The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yi
authors.affiliation: Department of Surgery, Beijing Hospital, Beijing, 100730, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China.|Department of Surgery, Beijing Hospital, Beijing, 100730, China.
authors.forename: Feiliang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, Japan.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
authors.affiliation: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Isaji
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China.
authors.forename: Ruomei
authors.initials: R
authors.lastname: Qi
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China. zhuxqyy@163.com.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Peking University Fifth School of Clinical Medicine, Beijing Hospital, Beijing, 100730, China. yanyangzhaobj@gmail.com.|The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China. yanyangzhaobj@gmail.com.
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D039564:Integrin alphaV / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D039564:Integrin alphaV; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1
keywords: Cell motility; Integrin; TGF-β1; miR-130b