Dysregulation of EZH2/miR-138-5p Axis Contributes to Radiosensitivity in Hepatocellular Carcinoma Cell by Downregulating Hypoxia-Inducible Factor 1 Alpha (HIF-1α)
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase involved in cell proliferation, invasion, angiogenesis, and metastasis in various cancers, including hepatocellular carcinoma (HCC). However, the role and molecular mechanisms of EZH2 in HCC radiosensitivity remain unclear. Here, we s...
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| Veröffentlicht in: | Oxidative medicine and cellular longevity 2022-08, Vol.2022, p.1-22 |
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| creator | Bai, Bing Liu, Ying Fu, Xue-Mei Qin, Hai-Yan Li, Gao-Kai Wang, Hai-Chen Sun, Shi-Long |
| description | Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase involved in cell proliferation, invasion, angiogenesis, and metastasis in various cancers, including hepatocellular carcinoma (HCC). However, the role and molecular mechanisms of EZH2 in HCC radiosensitivity remain unclear. Here, we show that EZH2 is upregulated in HCC cells and the aberrantly overexpressed EZH2 is associated with the poor prognosis of HCC patients. Using miRNA databases, we identified miR-138-5p as a regulator of EZH2. We also found that miR-138-5p was suppressed by EZH2-induced H3K27me3 in HCC cell lines. MiR-138-5p overexpression and EZH2 knockdown enhanced cellular radiosensitivity while inhibiting cell migration, invasion, and epithelial-mesenchymal transition (EMT). Analysis of RNA-seq datasets revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was the main enrichment pathway for differential genes after miR-138-5p overexpression or EZH2 knockdown. Expression level of HIF-1α was significantly suppressed after miR-138-5p overexpression or silencing of EZH2. HIF-1α silencing mitigated resistance of HCC cells and inhibited EMT. This study establishes the EZH2/miR-138-5p/HIF-1α as a potential therapeutic target for sensitizing HCC to radiotherapy. |
| doi_str_mv | 10.1155/2022/7608712 |
| format | Article |
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However, the role and molecular mechanisms of EZH2 in HCC radiosensitivity remain unclear. Here, we show that EZH2 is upregulated in HCC cells and the aberrantly overexpressed EZH2 is associated with the poor prognosis of HCC patients. Using miRNA databases, we identified miR-138-5p as a regulator of EZH2. We also found that miR-138-5p was suppressed by EZH2-induced H3K27me3 in HCC cell lines. MiR-138-5p overexpression and EZH2 knockdown enhanced cellular radiosensitivity while inhibiting cell migration, invasion, and epithelial-mesenchymal transition (EMT). Analysis of RNA-seq datasets revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was the main enrichment pathway for differential genes after miR-138-5p overexpression or EZH2 knockdown. Expression level of HIF-1α was significantly suppressed after miR-138-5p overexpression or silencing of EZH2. HIF-1α silencing mitigated resistance of HCC cells and inhibited EMT. This study establishes the EZH2/miR-138-5p/HIF-1α as a potential therapeutic target for sensitizing HCC to radiotherapy.</description><identifier>ISSN: 1942-0900</identifier><identifier>EISSN: 1942-0994</identifier><identifier>DOI: 10.1155/2022/7608712</identifier><identifier>PMID: 36071871</identifier><language>eng</language><publisher>New York: Hindawi</publisher><subject>Antibodies ; Cancer therapies ; Cell culture ; Clinical outcomes ; Efficiency ; Gene expression ; Hypoxia ; Liver cancer ; Lymphocytes ; Medical prognosis ; MicroRNAs ; Proteins ; Radiation therapy ; Wound healing</subject><ispartof>Oxidative medicine and cellular longevity, 2022-08, Vol.2022, p.1-22</ispartof><rights>Copyright © 2022 Bing Bai et al.</rights><rights>Copyright © 2022 Bing Bai et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2022 Bing Bai et al. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-a41cc708914e21cca783f7f5ec03f3aad8c5bbe2103e8a9ff59dca558fc6fb0b3</citedby><cites>FETCH-LOGICAL-c425t-a41cc708914e21cca783f7f5ec03f3aad8c5bbe2103e8a9ff59dca558fc6fb0b3</cites><orcidid>0000-0002-6335-8734 ; 0000-0003-2911-9681 ; 0000-0001-5198-3359 ; 0000-0002-0012-2062 ; 0000-0003-4199-5393 ; 0000-0002-6985-734X ; 0000-0002-9584-8551</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444475/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444475/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids></links><search><contributor>Cai, Lu</contributor><contributor>Lu Cai</contributor><creatorcontrib>Bai, Bing</creatorcontrib><creatorcontrib>Liu, Ying</creatorcontrib><creatorcontrib>Fu, Xue-Mei</creatorcontrib><creatorcontrib>Qin, Hai-Yan</creatorcontrib><creatorcontrib>Li, Gao-Kai</creatorcontrib><creatorcontrib>Wang, Hai-Chen</creatorcontrib><creatorcontrib>Sun, Shi-Long</creatorcontrib><title>Dysregulation of EZH2/miR-138-5p Axis Contributes to Radiosensitivity in Hepatocellular Carcinoma Cell by Downregulating Hypoxia-Inducible Factor 1 Alpha (HIF-1α)</title><title>Oxidative medicine and cellular longevity</title><description>Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase involved in cell proliferation, invasion, angiogenesis, and metastasis in various cancers, including hepatocellular carcinoma (HCC). 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However, the role and molecular mechanisms of EZH2 in HCC radiosensitivity remain unclear. Here, we show that EZH2 is upregulated in HCC cells and the aberrantly overexpressed EZH2 is associated with the poor prognosis of HCC patients. Using miRNA databases, we identified miR-138-5p as a regulator of EZH2. We also found that miR-138-5p was suppressed by EZH2-induced H3K27me3 in HCC cell lines. MiR-138-5p overexpression and EZH2 knockdown enhanced cellular radiosensitivity while inhibiting cell migration, invasion, and epithelial-mesenchymal transition (EMT). Analysis of RNA-seq datasets revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was the main enrichment pathway for differential genes after miR-138-5p overexpression or EZH2 knockdown. Expression level of HIF-1α was significantly suppressed after miR-138-5p overexpression or silencing of EZH2. HIF-1α silencing mitigated resistance of HCC cells and inhibited EMT. This study establishes the EZH2/miR-138-5p/HIF-1α as a potential therapeutic target for sensitizing HCC to radiotherapy.</abstract><cop>New York</cop><pub>Hindawi</pub><pmid>36071871</pmid><doi>10.1155/2022/7608712</doi><tpages>22</tpages><orcidid>https://orcid.org/0000-0002-6335-8734</orcidid><orcidid>https://orcid.org/0000-0003-2911-9681</orcidid><orcidid>https://orcid.org/0000-0001-5198-3359</orcidid><orcidid>https://orcid.org/0000-0002-0012-2062</orcidid><orcidid>https://orcid.org/0000-0003-4199-5393</orcidid><orcidid>https://orcid.org/0000-0002-6985-734X</orcidid><orcidid>https://orcid.org/0000-0002-9584-8551</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies Cancer therapies Cell culture Clinical outcomes Efficiency Gene expression Hypoxia Liver cancer Lymphocytes Medical prognosis MicroRNAs Proteins Radiation therapy Wound healing |
| title | Dysregulation of EZH2/miR-138-5p Axis Contributes to Radiosensitivity in Hepatocellular Carcinoma Cell by Downregulating Hypoxia-Inducible Factor 1 Alpha (HIF-1α) |
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