Cargando…

miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells

BACKGROUND: Accumulating evidence indicates that aberrant microRNA (miRNA) expression contributes to osteosarcoma progression. This study aimed to elucidate the association between miR-624-5p expression and osteosarcoma (OS) development and to investigate its underlying mechanism. METHODS: We analyz...

Descripción completa

Detalles Bibliográficos
Autores principales: Luo, Yongjun, Liu, Wei, Tang, Pengyu, Jiang, Dongdong, Gu, Changjiang, Huang, Yumin, Gong, Fangyi, Rong, Yuluo, Qian, Dingfei, Chen, Jian, Zhou, Zheng, Zhao, Shujie, Wang, Jiaxing, Xu, Tao, Wei, Yongzhong, Yin, Guoyong, Fan, Jin, Cai, Weihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907337/
https://www.ncbi.nlm.nih.gov/pubmed/31829261
http://dx.doi.org/10.1186/s13046-019-1491-6
_version_ 1783478524193013760
author Luo, Yongjun
Liu, Wei
Tang, Pengyu
Jiang, Dongdong
Gu, Changjiang
Huang, Yumin
Gong, Fangyi
Rong, Yuluo
Qian, Dingfei
Chen, Jian
Zhou, Zheng
Zhao, Shujie
Wang, Jiaxing
Xu, Tao
Wei, Yongzhong
Yin, Guoyong
Fan, Jin
Cai, Weihua
author_facet Luo, Yongjun
Liu, Wei
Tang, Pengyu
Jiang, Dongdong
Gu, Changjiang
Huang, Yumin
Gong, Fangyi
Rong, Yuluo
Qian, Dingfei
Chen, Jian
Zhou, Zheng
Zhao, Shujie
Wang, Jiaxing
Xu, Tao
Wei, Yongzhong
Yin, Guoyong
Fan, Jin
Cai, Weihua
author_sort Luo, Yongjun
collection PubMed
description BACKGROUND: Accumulating evidence indicates that aberrant microRNA (miRNA) expression contributes to osteosarcoma progression. This study aimed to elucidate the association between miR-624-5p expression and osteosarcoma (OS) development and to investigate its underlying mechanism. METHODS: We analyzed GSE65071 from the GEO database and found miR-624-5p was the most upregulated miRNA. The expression of miR-624-5p and its specific target gene were determined in human OS specimens and cell lines by RT-PCR and western blot. The effects of miR-624-5p depletion or ectopic expression on OS proliferation, migration and invasion were evaluated in vitro using CCK-8 proliferation assay, colony formation assay, transwell assay, would-healing assay and 3D spheroid BME cell invasion assay respectively. We investigated in vivo effects of miR-624-5p using a mouse tumorigenicity model. Besides, luciferase reporter assays were employed to identify interactions between miR-624-5p and its specific target gene. RESULTS: miR-624-5p expression was upregulated in OS cells and tissues, and overexpressing miR-624-5p led to a higher malignant level of OS, including cell proliferation, migration and invasion in vitro and in vivo. Protein tyrosine phosphatase receptor type B (PTPRB) was negatively correlated with miR-624-5p expression in OS tissues. Using the luciferase reporter assay and Western blotting, PTPRB was confirmed as a downstream target of miR-624-5p. PTPRB restored the effects of miR-624-5p on OS migration and invasion. The Hippo signaling pathway was identified as being involved in the miR-624-5p/PTPRB axis. CONCLUSIONS: In conclusion, our results suggest that miR-624-5p is a negative regulator of PTPRB and a risk factor for tumor metastasis in OS progression.
format Online
Article
Text
id pubmed-6907337
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-69073372019-12-19 miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells Luo, Yongjun Liu, Wei Tang, Pengyu Jiang, Dongdong Gu, Changjiang Huang, Yumin Gong, Fangyi Rong, Yuluo Qian, Dingfei Chen, Jian Zhou, Zheng Zhao, Shujie Wang, Jiaxing Xu, Tao Wei, Yongzhong Yin, Guoyong Fan, Jin Cai, Weihua J Exp Clin Cancer Res Research BACKGROUND: Accumulating evidence indicates that aberrant microRNA (miRNA) expression contributes to osteosarcoma progression. This study aimed to elucidate the association between miR-624-5p expression and osteosarcoma (OS) development and to investigate its underlying mechanism. METHODS: We analyzed GSE65071 from the GEO database and found miR-624-5p was the most upregulated miRNA. The expression of miR-624-5p and its specific target gene were determined in human OS specimens and cell lines by RT-PCR and western blot. The effects of miR-624-5p depletion or ectopic expression on OS proliferation, migration and invasion were evaluated in vitro using CCK-8 proliferation assay, colony formation assay, transwell assay, would-healing assay and 3D spheroid BME cell invasion assay respectively. We investigated in vivo effects of miR-624-5p using a mouse tumorigenicity model. Besides, luciferase reporter assays were employed to identify interactions between miR-624-5p and its specific target gene. RESULTS: miR-624-5p expression was upregulated in OS cells and tissues, and overexpressing miR-624-5p led to a higher malignant level of OS, including cell proliferation, migration and invasion in vitro and in vivo. Protein tyrosine phosphatase receptor type B (PTPRB) was negatively correlated with miR-624-5p expression in OS tissues. Using the luciferase reporter assay and Western blotting, PTPRB was confirmed as a downstream target of miR-624-5p. PTPRB restored the effects of miR-624-5p on OS migration and invasion. The Hippo signaling pathway was identified as being involved in the miR-624-5p/PTPRB axis. CONCLUSIONS: In conclusion, our results suggest that miR-624-5p is a negative regulator of PTPRB and a risk factor for tumor metastasis in OS progression. BioMed Central 2019-12-11 /pmc/articles/PMC6907337/ /pubmed/31829261 http://dx.doi.org/10.1186/s13046-019-1491-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Luo, Yongjun
Liu, Wei
Tang, Pengyu
Jiang, Dongdong
Gu, Changjiang
Huang, Yumin
Gong, Fangyi
Rong, Yuluo
Qian, Dingfei
Chen, Jian
Zhou, Zheng
Zhao, Shujie
Wang, Jiaxing
Xu, Tao
Wei, Yongzhong
Yin, Guoyong
Fan, Jin
Cai, Weihua
miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells
title miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells
title_full miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells
title_fullStr miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells
title_full_unstemmed miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells
title_short miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells
title_sort mir-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting ptprb in osteosarcoma cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907337/
https://www.ncbi.nlm.nih.gov/pubmed/31829261
http://dx.doi.org/10.1186/s13046-019-1491-6
work_keys_str_mv AT luoyongjun mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT liuwei mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT tangpengyu mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT jiangdongdong mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT guchangjiang mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT huangyumin mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT gongfangyi mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT rongyuluo mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT qiandingfei mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT chenjian mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT zhouzheng mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT zhaoshujie mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT wangjiaxing mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT xutao mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT weiyongzhong mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT yinguoyong mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT fanjin mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells
AT caiweihua mir6245ppromotedtumorigenesisandmetastasisbysuppressinghipposignalingthroughtargetingptprbinosteosarcomacells