Long non‐coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2‐mediated epigenetic modification
Abstract Gemcitabine resistance (GR) in pancreatic cancer (PC) results in poor patient outcomes. SMAD family member (Smad4) dysregulation is a significant role of GR in PC, and EZH2 is involved in Smad4 expression in tumor progression. Interestingly, lncRNA small nucleolar RNA host gene 16 (SNHG16)...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | Kaohsiung Journal of Medical Sciences |
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| Online Access: | https://doi.org/10.1002/kjm2.12574 |
| _version_ | 1828106802158370816 |
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| author | Yi Yu Yu‐Feng Zou Run‐Qi Hong Wen‐Jie Chen Liang Chen Wen‐Qi Chen Hui‐Peng Wang Yuan Yu |
| author_facet | Yi Yu Yu‐Feng Zou Run‐Qi Hong Wen‐Jie Chen Liang Chen Wen‐Qi Chen Hui‐Peng Wang Yuan Yu |
| author_sort | Yi Yu |
| collection | DOAJ |
| description | Abstract Gemcitabine resistance (GR) in pancreatic cancer (PC) results in poor patient outcomes. SMAD family member (Smad4) dysregulation is a significant role of GR in PC, and EZH2 is involved in Smad4 expression in tumor progression. Interestingly, lncRNA small nucleolar RNA host gene 16 (SNHG16) might interact with EZH2, indicating a potential pathway to overcome gemcitabine‐resistant PC progression. We investigated the role of the SNHG16/EZH2/Smad4 pathway in gemcitabine‐resistant PC cells (PANC‐1/GR and SW1990/GR). First, we found that SNHG16 was upregulated both in wild‐type PC cells and in gemcitabine‐resistant PC cells. SNHG16 overexpression reduced gemcitabine cytotoxicity and apoptosis in PC cells. Meanwhile, SNHG16 upregulation caused p‐Akt elevation and Smad4 reduction. However, SNHG16 silencing induced the opposite trend. Then, we found that EZH2 was enriched in SNHG16 based on RIP and RNA pulldown. In particular, SNHG16 overexpression promoted the interaction between EZH2 and the Smad4 promoter according to Chromatin immunoprecipitation‐quantitative polymerase chain reaction. Finally, both EZH2 inhibition and Smad4 upregulation increased gemcitabine cytotoxicity and apoptosis in PC cells during SNHG16 overexpression. Moreover, both treatments decreased p‐Akt and increased Smad4. Collectively, lncRNA SNHG16 decreased Smad4 to induce GR in PC via EZH2‐mediated epigenetic modification. |
| first_indexed | 2024-04-11T10:21:37Z |
| format | Article |
| id | doaj.art-8e18f71a194d4ed1a132f5e5acb58da2 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-04-11T10:21:37Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-8e18f71a194d4ed1a132f5e5acb58da22022-12-22T04:29:43ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502022-10-01381098199110.1002/kjm2.12574Long non‐coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2‐mediated epigenetic modificationYi Yu0Yu‐Feng Zou1Run‐Qi Hong2Wen‐Jie Chen3Liang Chen4Wen‐Qi Chen5Hui‐Peng Wang6Yuan Yu7Department of Pediatrics Ruijin Hospital, Shanghai Jiaotong University, School of Medicine Shanghai ChinaDepartment of General Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai ChinaDepartment of General Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai ChinaDepartment of General Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai ChinaDepartment of General Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai ChinaDepartment of General Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai ChinaDepartment of General Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai ChinaDepartment of General Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai ChinaAbstract Gemcitabine resistance (GR) in pancreatic cancer (PC) results in poor patient outcomes. SMAD family member (Smad4) dysregulation is a significant role of GR in PC, and EZH2 is involved in Smad4 expression in tumor progression. Interestingly, lncRNA small nucleolar RNA host gene 16 (SNHG16) might interact with EZH2, indicating a potential pathway to overcome gemcitabine‐resistant PC progression. We investigated the role of the SNHG16/EZH2/Smad4 pathway in gemcitabine‐resistant PC cells (PANC‐1/GR and SW1990/GR). First, we found that SNHG16 was upregulated both in wild‐type PC cells and in gemcitabine‐resistant PC cells. SNHG16 overexpression reduced gemcitabine cytotoxicity and apoptosis in PC cells. Meanwhile, SNHG16 upregulation caused p‐Akt elevation and Smad4 reduction. However, SNHG16 silencing induced the opposite trend. Then, we found that EZH2 was enriched in SNHG16 based on RIP and RNA pulldown. In particular, SNHG16 overexpression promoted the interaction between EZH2 and the Smad4 promoter according to Chromatin immunoprecipitation‐quantitative polymerase chain reaction. Finally, both EZH2 inhibition and Smad4 upregulation increased gemcitabine cytotoxicity and apoptosis in PC cells during SNHG16 overexpression. Moreover, both treatments decreased p‐Akt and increased Smad4. Collectively, lncRNA SNHG16 decreased Smad4 to induce GR in PC via EZH2‐mediated epigenetic modification.https://doi.org/10.1002/kjm2.12574EZH2gemcitabine resistancelncRNA SNHG16pancreatic cancerSmad4 |
| spellingShingle | Yi Yu Yu‐Feng Zou Run‐Qi Hong Wen‐Jie Chen Liang Chen Wen‐Qi Chen Hui‐Peng Wang Yuan Yu Long non‐coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2‐mediated epigenetic modification Kaohsiung Journal of Medical Sciences EZH2 gemcitabine resistance lncRNA SNHG16 pancreatic cancer Smad4 |
| title | Long non‐coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2‐mediated epigenetic modification |
| title_full | Long non‐coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2‐mediated epigenetic modification |
| title_fullStr | Long non‐coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2‐mediated epigenetic modification |
| title_full_unstemmed | Long non‐coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2‐mediated epigenetic modification |
| title_short | Long non‐coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2‐mediated epigenetic modification |
| title_sort | long non coding rna snhg16 decreased smad4 to induce gemcitabine resistance in pancreatic cancer via ezh2 mediated epigenetic modification |
| topic | EZH2 gemcitabine resistance lncRNA SNHG16 pancreatic cancer Smad4 |
| url | https://doi.org/10.1002/kjm2.12574 |
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