Cargando…
miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer
MicroRNAs (miRNAs) are non-coding small RNAs that function as negative regulators of gene expression involving in the tumor biology. ATP citrate lyase (ACLY), a key enzyme initiating de novo lipid synthesis, has been found to be upregulated in cancer cells, and its inhibition causes suppressive effe...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190093/ https://www.ncbi.nlm.nih.gov/pubmed/27317765 http://dx.doi.org/10.18632/oncotarget.10020 |
_version_ | 1782487350529490944 |
---|---|
author | Xin, Mei Qiao, Zhiguang Li, Jing Liu, Jianjun Song, Shaoli Zhao, Xiaoping Miao, Ping Tang, Tingting Wang, Lei Liu, Weichun Yang, Xiaodi Dai, Kerong Huang, Gang |
author_facet | Xin, Mei Qiao, Zhiguang Li, Jing Liu, Jianjun Song, Shaoli Zhao, Xiaoping Miao, Ping Tang, Tingting Wang, Lei Liu, Weichun Yang, Xiaodi Dai, Kerong Huang, Gang |
author_sort | Xin, Mei |
collection | PubMed |
description | MicroRNAs (miRNAs) are non-coding small RNAs that function as negative regulators of gene expression involving in the tumor biology. ATP citrate lyase (ACLY), a key enzyme initiating de novo lipid synthesis, has been found to be upregulated in cancer cells, and its inhibition causes suppressive effects in a variety of tumors. At present, although several ACLY inhibitors have been reported, the potential role of miRNAs in interfering ACLY still needs further clarification. Herein, four different types of tumor cells including osteosarcoma, prostate, cervical and lung cancers were adopted in our study, and we have demonstrated that miR-22 directly downregulated ACLY. Moreover, miR-22 was proved to attenuate cancer cell proliferation and invasion, as well as promote cell apoptosis via inhibiting ACLY. Additionally, we confirmed the higher ACLY protein levels and the lower miR-22 expressions in hundreds of clinical samples of the four primary tumors, and a negative correlation relationship between ACLY and miR-22 was clarified. Finally, in the four animal models, we found that along with the loss of the ACLY expression, the miR-22-treated mice developed rather smaller tumors, less probabilities of distant metastasis, and fairly longer survivals. De novo lipogenesis suppression triggered by miR-22-ACLY axis may contribute to the inhibition of tumor growth and metastasis. These findings provide unequivocal proofs that miR-22 is responsible for the posttranscriptional regulation of ACLY, which yields promising therapeutic effects in osteosarcoma, prostate, cervical and lung cancers. |
format | Online Article Text |
id | pubmed-5190093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-51900932017-01-05 miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer Xin, Mei Qiao, Zhiguang Li, Jing Liu, Jianjun Song, Shaoli Zhao, Xiaoping Miao, Ping Tang, Tingting Wang, Lei Liu, Weichun Yang, Xiaodi Dai, Kerong Huang, Gang Oncotarget Research Paper MicroRNAs (miRNAs) are non-coding small RNAs that function as negative regulators of gene expression involving in the tumor biology. ATP citrate lyase (ACLY), a key enzyme initiating de novo lipid synthesis, has been found to be upregulated in cancer cells, and its inhibition causes suppressive effects in a variety of tumors. At present, although several ACLY inhibitors have been reported, the potential role of miRNAs in interfering ACLY still needs further clarification. Herein, four different types of tumor cells including osteosarcoma, prostate, cervical and lung cancers were adopted in our study, and we have demonstrated that miR-22 directly downregulated ACLY. Moreover, miR-22 was proved to attenuate cancer cell proliferation and invasion, as well as promote cell apoptosis via inhibiting ACLY. Additionally, we confirmed the higher ACLY protein levels and the lower miR-22 expressions in hundreds of clinical samples of the four primary tumors, and a negative correlation relationship between ACLY and miR-22 was clarified. Finally, in the four animal models, we found that along with the loss of the ACLY expression, the miR-22-treated mice developed rather smaller tumors, less probabilities of distant metastasis, and fairly longer survivals. De novo lipogenesis suppression triggered by miR-22-ACLY axis may contribute to the inhibition of tumor growth and metastasis. These findings provide unequivocal proofs that miR-22 is responsible for the posttranscriptional regulation of ACLY, which yields promising therapeutic effects in osteosarcoma, prostate, cervical and lung cancers. Impact Journals LLC 2016-06-14 /pmc/articles/PMC5190093/ /pubmed/27317765 http://dx.doi.org/10.18632/oncotarget.10020 Text en Copyright: © 2016 Xin et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Xin, Mei Qiao, Zhiguang Li, Jing Liu, Jianjun Song, Shaoli Zhao, Xiaoping Miao, Ping Tang, Tingting Wang, Lei Liu, Weichun Yang, Xiaodi Dai, Kerong Huang, Gang miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer |
title | miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer |
title_full | miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer |
title_fullStr | miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer |
title_full_unstemmed | miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer |
title_short | miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer |
title_sort | mir-22 inhibits tumor growth and metastasis by targeting atp citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190093/ https://www.ncbi.nlm.nih.gov/pubmed/27317765 http://dx.doi.org/10.18632/oncotarget.10020 |
work_keys_str_mv | AT xinmei mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT qiaozhiguang mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT lijing mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT liujianjun mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT songshaoli mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT zhaoxiaoping mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT miaoping mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT tangtingting mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT wanglei mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT liuweichun mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT yangxiaodi mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT daikerong mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer AT huanggang mir22inhibitstumorgrowthandmetastasisbytargetingatpcitratelyaseevidenceinosteosarcomaprostatecancercervicalcancerandlungcancer |