Yin Leng1, Zhixian Chen2, Hui Ding1, Xiaoxu Zhao3, Li Qin4, Yunlong Pan5. 1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, No. 601, Huangpu Avenue, Guangzhou, 510632, Guangdong, People's Republic of China. 2. Department of Oncology, Fuda Cancer Hospital, Jinan University, Guangzhou, 510665, People's Republic of China. 3. Medical Department, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, People's Republic of China. 4. Department of Histology and Embryology, Medical School of Jinan University, Guangzhou, 510632, People's Republic of China. 5. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, No. 601, Huangpu Avenue, Guangzhou, 510632, Guangdong, People's Republic of China. pan_panyunlong@163.com.
Abstract
BACKGROUND: Recent studies have reported the involvement of microRNA-29 (miR-29) family members in human cancers through their ability to regulate cellular functions. The present study investigated biological function of miR-29b in colorectal cancer (CRC). METHODS: CRC tissues and adjacent normal tissues were collected and the expression of ETV4 and miR-29b in the tissues were identified. The relationship between ETV4 and miR-29b or ETV4 expression and the EGFR promoter was identified using dual-luciferase reporter gene and CHIP assays. The proliferation, invasion, migration, and apoptosis of CRC HCT116 cells were assayed using MTT assay, Scratch test, Transwell assay, and flow cytometry, respectively. Also, expression of epithelial-mesenchymal transition (EMT) markers, angiogenic factors, and vasculogenic mimicry formation were evaluated using RT-qPCR and Western blot. RESULTS: ETV4 was upregulated, while miR-29b expression was decreased in CRC tissues. ETV4 was identified as a target gene of miR-29b, which in turn inactivated the ERK signaling pathway by targeting ETV4 and inhibiting EGFR transcription. Transfection with miR-29b mimic, siRNA-ETV4, or ERK signaling pathway inhibitor U0126 increased expression of E-cadherin and TSP-1, and CRC cell apoptosis, yet reduced expression of ERK1/2, MMP-2, MMP-9, Vimentin, and VEGF, as well as inhibiting EMT, angiogenesis, and CRC cell migration and invasion. The EMT, angiogenesis and cancer progression induced by miR-29b inhibitor were reversed by siRNA-mediated ETV4 silencing. CONCLUSIONS: miR-29b suppresses angiogenesis and EMT in CRC via the ETV4/ERK/EGFR axis.
BACKGROUND: Recent studies have reported the involvement of microRNA-29 (miR-29) family members in humancancers through their ability to regulate cellular functions. The present study investigated biological function of miR-29b in colorectal cancer (CRC). METHODS: CRC tissues and adjacent normal tissues were collected and the expression of ETV4 and miR-29b in the tissues were identified. The relationship between ETV4 and miR-29b or ETV4 expression and the EGFR promoter was identified using dual-luciferase reporter gene and CHIP assays. The proliferation, invasion, migration, and apoptosis of CRC HCT116 cells were assayed using MTT assay, Scratch test, Transwell assay, and flow cytometry, respectively. Also, expression of epithelial-mesenchymal transition (EMT) markers, angiogenic factors, and vasculogenic mimicry formation were evaluated using RT-qPCR and Western blot. RESULTS:ETV4 was upregulated, while miR-29b expression was decreased in CRC tissues. ETV4 was identified as a target gene of miR-29b, which in turn inactivated the ERKsignaling pathway by targeting ETV4 and inhibiting EGFR transcription. Transfection with miR-29b mimic, siRNA-ETV4, or ERKsignaling pathway inhibitor U0126 increased expression of E-cadherin and TSP-1, and CRC cell apoptosis, yet reduced expression of ERK1/2, MMP-2, MMP-9, Vimentin, and VEGF, as well as inhibiting EMT, angiogenesis, and CRC cell migration and invasion. The EMT, angiogenesis and cancer progression induced by miR-29b inhibitor were reversed by siRNA-mediated ETV4silencing. CONCLUSIONS:miR-29b suppresses angiogenesis and EMT in CRC via the ETV4/ERK/EGFR axis.
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