Y R Park1,2, S L Kim1,2, M R Lee2,3, S Y Seo1,2, J H Lee4, S H Kim1,2, I H Kim1,2, S O Lee1,2, S T Lee1,2, Sang Wook Kim5,6. 1. Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Republic of Korea. 2. Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju, Jeonbuk, 54896, Republic of Korea. 3. Department of Surgery, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Republic of Korea. 4. Department of Preventive Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea. 5. Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Republic of Korea. clickm@jbnu.ac.kr. 6. Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju, Jeonbuk, 54896, Republic of Korea. clickm@jbnu.ac.kr.
Abstract
PURPOSE: Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, and many oncogenes and tumor suppressor genes are involved in CRC. MicroRNAs (miRNAs) are small non-coding RNAs that can negatively regulate gene expression. Previous studies have revealed that miRNAs regulate the development and progression of many cancers. In this study, we investigated the role of microRNA-30a-5p (miR-30a) in CRC and its unknown mechanisms. METHODS: qRT-PCR was used to detect miR-30a and TM4SF1 mRNA expression in CRC specimens and cell lines. CRC cell migration and invasion were assessed after transfection with miR-30a or TM4SF1 using wound healing and trans-well migration and invasion assays. Transmembrane-4-L-six-family protein (TM4SF1) was validated as a target of miR-30a in CRC through luciferase reporter assay and bioinformatics algorithms. Moreover, two EMT regulators, E-cadherin and VEGF, were also identified using Western blotting and immunohistochemistry. RESULTS: We found that miR-30a was down-regulated in CRC tumor tissues and cell lines, and miR-30a was inversely associated with advanced stage and lymph node metastatic status compared with normal tissues. miR-30a decreased migration and invasion in CRC cell lines, and miR-30a overexpression not only down-regulated TM4SF1 mRNA and protein expression, but also inhibited the expression of VEGF and enhanced expression of E-cadherin. We also showed that TM4SF1 was up-regulated in CRC tumor specimens compared with adjacent normal tissues, and TM4SF1 expression was significantly associated with advanced stage and lymph node status compared with adjacent normal tissues. CONCLUSIONS: These results suggest that miR-30a is an important regulator of TM4SF1, VEGF, and E-cadherin for CRC lymph node metastasis, a potential new therapeutic target in CRC.
PURPOSE:Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, and many oncogenes and tumor suppressor genes are involved in CRC. MicroRNAs (miRNAs) are small non-coding RNAs that can negatively regulate gene expression. Previous studies have revealed that miRNAs regulate the development and progression of many cancers. In this study, we investigated the role of microRNA-30a-5p (miR-30a) in CRC and its unknown mechanisms. METHODS: qRT-PCR was used to detect miR-30a and TM4SF1 mRNA expression in CRC specimens and cell lines. CRC cell migration and invasion were assessed after transfection with miR-30a or TM4SF1 using wound healing and trans-well migration and invasion assays. Transmembrane-4-L-six-family protein (TM4SF1) was validated as a target of miR-30a in CRC through luciferase reporter assay and bioinformatics algorithms. Moreover, two EMT regulators, E-cadherin and VEGF, were also identified using Western blotting and immunohistochemistry. RESULTS: We found that miR-30a was down-regulated in CRC tumor tissues and cell lines, and miR-30a was inversely associated with advanced stage and lymph node metastatic status compared with normal tissues. miR-30a decreased migration and invasion in CRC cell lines, and miR-30a overexpression not only down-regulated TM4SF1 mRNA and protein expression, but also inhibited the expression of VEGF and enhanced expression of E-cadherin. We also showed that TM4SF1 was up-regulated in CRC tumor specimens compared with adjacent normal tissues, and TM4SF1 expression was significantly associated with advanced stage and lymph node status compared with adjacent normal tissues. CONCLUSIONS: These results suggest that miR-30a is an important regulator of TM4SF1, VEGF, and E-cadherin for CRC lymph node metastasis, a potential new therapeutic target in CRC.
Entities:
Keywords:
Colorectal cancer; Metastasis; Transmembrane-4-L-six-family protein 1; miR-30a
Authors: R Visone; P Pallante; A Vecchione; R Cirombella; M Ferracin; A Ferraro; S Volinia; S Coluzzi; V Leone; E Borbone; C-G Liu; F Petrocca; G Troncone; G A Calin; A Scarpa; C Colato; G Tallini; M Santoro; C M Croce; A Fusco Journal: Oncogene Date: 2007-06-11 Impact factor: 9.867
Authors: Young Ran Park; Seung Young Seo; Se Lim Kim; Shi Mao Zhu; Sungkun Chun; Jung-Mi Oh; Min Ro Lee; Seong Hun Kim; In Hee Kim; Seung Ok Lee; Soo Teik Lee; Sang Wook Kim Journal: Biosci Rep Date: 2018-09-19 Impact factor: 3.840