Cargando…
miR-302a-3p Promotes Radiotherapy Sensitivity of Hepatocellular Carcinoma by Regulating Cell Cycle via MCL1
BACKGROUND: The relationship between tumor suppressor gene miR-302a-3p and radiotherapy for hepatocellular carcinoma (HCC) remains unclear. This study intended to illustrate the molecular mechanism how miR-302a-3p regulated radiotherapy sensitivity of HCC. METHODS: miR-302a-3p expression in HCC tiss...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576429/ https://www.ncbi.nlm.nih.gov/pubmed/36262872 http://dx.doi.org/10.1155/2022/1450098 |
_version_ | 1784811525213519872 |
---|---|
author | Yang, Zifeng Zhang, Menglong Zhang, Jian Chu, Cunkun Hu, Bijuan Huang, Liyin |
author_facet | Yang, Zifeng Zhang, Menglong Zhang, Jian Chu, Cunkun Hu, Bijuan Huang, Liyin |
author_sort | Yang, Zifeng |
collection | PubMed |
description | BACKGROUND: The relationship between tumor suppressor gene miR-302a-3p and radiotherapy for hepatocellular carcinoma (HCC) remains unclear. This study intended to illustrate the molecular mechanism how miR-302a-3p regulated radiotherapy sensitivity of HCC. METHODS: miR-302a-3p expression in HCC tissues and cells was examined by qRT-PCR. The effect of miR-302a-3p on HCC radiotherapy sensitivity were detected by CCK-8, colony formation, and flow cytometry assays. The expression levels of cell cycle-related proteins were detected by Western blot. The influence of miR-302a-3p on radiotherapy sensitivity of HCC was further investigated via cell cycle inhibitor (Caudatin) treatment. The target gene (MCL1) of miR-302a-3p was obtained by bioinformatics analysis, and their binding relationship was confirmed by RNA-binding protein immunoprecipitation assay. The mechanisms of miR-302a-3p regulating cell cycle and affecting radiotherapy sensitivity of HCC cells through MCL1 were further explored through the rescue experiments. RESULTS: miR-302a-3p expression was remarkably reduced in radiotherapy-resistant tissues and cells of HCC. miR-302a-3p overexpression restored sensitivity of radiotherapy-resistant HCC cells to radiotherapy. Treatment with cell cycle inhibitor Caudatin could reverse suppressive effect of miR-302a-3p downregulation on sensitivity of HCC to radiotherapy. Additionally, miR-302a-3p could restrain MCL1 expression. In vitro cell assays further revealed that miR-302a-3p/MCL1 axis could enhance radiotherapy sensitivity of HCC cells by inducing G0/G1 arrest. CONCLUSIONS: miR-302a-3p facilitated radiotherapy sensitivity of HCC cells by regulating cell cycle via MCL1, which provided a new underlying target for radiotherapy resistance of HCC patients. |
format | Online Article Text |
id | pubmed-9576429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-95764292022-10-18 miR-302a-3p Promotes Radiotherapy Sensitivity of Hepatocellular Carcinoma by Regulating Cell Cycle via MCL1 Yang, Zifeng Zhang, Menglong Zhang, Jian Chu, Cunkun Hu, Bijuan Huang, Liyin Comput Math Methods Med Research Article BACKGROUND: The relationship between tumor suppressor gene miR-302a-3p and radiotherapy for hepatocellular carcinoma (HCC) remains unclear. This study intended to illustrate the molecular mechanism how miR-302a-3p regulated radiotherapy sensitivity of HCC. METHODS: miR-302a-3p expression in HCC tissues and cells was examined by qRT-PCR. The effect of miR-302a-3p on HCC radiotherapy sensitivity were detected by CCK-8, colony formation, and flow cytometry assays. The expression levels of cell cycle-related proteins were detected by Western blot. The influence of miR-302a-3p on radiotherapy sensitivity of HCC was further investigated via cell cycle inhibitor (Caudatin) treatment. The target gene (MCL1) of miR-302a-3p was obtained by bioinformatics analysis, and their binding relationship was confirmed by RNA-binding protein immunoprecipitation assay. The mechanisms of miR-302a-3p regulating cell cycle and affecting radiotherapy sensitivity of HCC cells through MCL1 were further explored through the rescue experiments. RESULTS: miR-302a-3p expression was remarkably reduced in radiotherapy-resistant tissues and cells of HCC. miR-302a-3p overexpression restored sensitivity of radiotherapy-resistant HCC cells to radiotherapy. Treatment with cell cycle inhibitor Caudatin could reverse suppressive effect of miR-302a-3p downregulation on sensitivity of HCC to radiotherapy. Additionally, miR-302a-3p could restrain MCL1 expression. In vitro cell assays further revealed that miR-302a-3p/MCL1 axis could enhance radiotherapy sensitivity of HCC cells by inducing G0/G1 arrest. CONCLUSIONS: miR-302a-3p facilitated radiotherapy sensitivity of HCC cells by regulating cell cycle via MCL1, which provided a new underlying target for radiotherapy resistance of HCC patients. Hindawi 2022-10-10 /pmc/articles/PMC9576429/ /pubmed/36262872 http://dx.doi.org/10.1155/2022/1450098 Text en Copyright © 2022 Zifeng Yang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yang, Zifeng Zhang, Menglong Zhang, Jian Chu, Cunkun Hu, Bijuan Huang, Liyin miR-302a-3p Promotes Radiotherapy Sensitivity of Hepatocellular Carcinoma by Regulating Cell Cycle via MCL1 |
title | miR-302a-3p Promotes Radiotherapy Sensitivity of Hepatocellular Carcinoma by Regulating Cell Cycle via MCL1 |
title_full | miR-302a-3p Promotes Radiotherapy Sensitivity of Hepatocellular Carcinoma by Regulating Cell Cycle via MCL1 |
title_fullStr | miR-302a-3p Promotes Radiotherapy Sensitivity of Hepatocellular Carcinoma by Regulating Cell Cycle via MCL1 |
title_full_unstemmed | miR-302a-3p Promotes Radiotherapy Sensitivity of Hepatocellular Carcinoma by Regulating Cell Cycle via MCL1 |
title_short | miR-302a-3p Promotes Radiotherapy Sensitivity of Hepatocellular Carcinoma by Regulating Cell Cycle via MCL1 |
title_sort | mir-302a-3p promotes radiotherapy sensitivity of hepatocellular carcinoma by regulating cell cycle via mcl1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576429/ https://www.ncbi.nlm.nih.gov/pubmed/36262872 http://dx.doi.org/10.1155/2022/1450098 |
work_keys_str_mv | AT yangzifeng mir302a3ppromotesradiotherapysensitivityofhepatocellularcarcinomabyregulatingcellcycleviamcl1 AT zhangmenglong mir302a3ppromotesradiotherapysensitivityofhepatocellularcarcinomabyregulatingcellcycleviamcl1 AT zhangjian mir302a3ppromotesradiotherapysensitivityofhepatocellularcarcinomabyregulatingcellcycleviamcl1 AT chucunkun mir302a3ppromotesradiotherapysensitivityofhepatocellularcarcinomabyregulatingcellcycleviamcl1 AT hubijuan mir302a3ppromotesradiotherapysensitivityofhepatocellularcarcinomabyregulatingcellcycleviamcl1 AT huangliyin mir302a3ppromotesradiotherapysensitivityofhepatocellularcarcinomabyregulatingcellcycleviamcl1 |