lncRNA DUXAP8 Facilitates Multiple Malignant Phenotypes and Resistance to PARP Inhibitor in HCC via Upregulating FOXM1
In this study, we examined the clinical significance and molecular mechanisms of a long non-coding RNA (lncRNA), double homeobox A pseudogene 8 (DUXAP8) in hepatocellular carcinoma (HCC). DUXAP8 expression was compared using quantitative real-time PCR in HCC versus adjacent tissues and in HCC cell l...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-12-01
|
| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770520301613 |
| _version_ | 1831523786196779008 |
|---|---|
| author | Yu Hu Xian Zhang Hong-Yan Zai Wei Jiang Liang Xiao Qin Zhu |
| author_facet | Yu Hu Xian Zhang Hong-Yan Zai Wei Jiang Liang Xiao Qin Zhu |
| author_sort | Yu Hu |
| collection | DOAJ |
| description | In this study, we examined the clinical significance and molecular mechanisms of a long non-coding RNA (lncRNA), double homeobox A pseudogene 8 (DUXAP8) in hepatocellular carcinoma (HCC). DUXAP8 expression was compared using quantitative real-time PCR in HCC versus adjacent tissues and in HCC cell lines versus normal hepatic epithelial cells. The correlations between DUXAP8 level and clinicopathological features were analyzed. Assays including MTT, colony-forming analysis, Transwell assay, western blot, xenograft formation, experimental metastasis, luciferase assay, RNA pull-down, and RNA immunoprecipitation were used to examine DUXAP8-induced malignant phenotypes, its regulation on forkhead box protein M1 (FOXM1), and the importance of FOXM1 in mediating DUXAP8 phenotypes. Our results showed that DUXAP8 was significantly upregulated in HCC tissues or cell lines associated with tumors of advanced grades, tumors that were positive for lymph node metastasis, and patients with poor overall survival. DUAXP8 was essential in maintaining multiple malignant phenotypes (including resistance to olaparib) both in vitro and in vivo. Mechanistically, DUXAP8 upregulated FOXM1 expression by sponging miR-485-5p and interacting with the RNA-binding protein Fused in Sarcoma (FUS). Functionally, FOXM1 essentially mediated the oncogenic phenotypes of DUXAP8. Collectively, DUXAP8 acts through two distinct mechanisms to upregulate FOXM1 and becomes a pleotropic oncogenic lncRNA in HCC. |
| first_indexed | 2024-12-14T18:00:20Z |
| format | Article |
| id | doaj.art-f2cdc28d9a1245e9aa7b66d0045221f1 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-14T18:00:20Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-f2cdc28d9a1245e9aa7b66d0045221f12022-12-21T22:52:28ZengElsevierMolecular Therapy: Oncolytics2372-77052020-12-0119308322lncRNA DUXAP8 Facilitates Multiple Malignant Phenotypes and Resistance to PARP Inhibitor in HCC via Upregulating FOXM1Yu Hu0Xian Zhang1Hong-Yan Zai2Wei Jiang3Liang Xiao4Qin Zhu5Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. ChinaDepartment of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410008, Hunan Province, P.R. ChinaDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. ChinaDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. ChinaDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. ChinaDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China; Corresponding author: Qin Zhu, MD, Department of General Surgery, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan Province, P.R. China.In this study, we examined the clinical significance and molecular mechanisms of a long non-coding RNA (lncRNA), double homeobox A pseudogene 8 (DUXAP8) in hepatocellular carcinoma (HCC). DUXAP8 expression was compared using quantitative real-time PCR in HCC versus adjacent tissues and in HCC cell lines versus normal hepatic epithelial cells. The correlations between DUXAP8 level and clinicopathological features were analyzed. Assays including MTT, colony-forming analysis, Transwell assay, western blot, xenograft formation, experimental metastasis, luciferase assay, RNA pull-down, and RNA immunoprecipitation were used to examine DUXAP8-induced malignant phenotypes, its regulation on forkhead box protein M1 (FOXM1), and the importance of FOXM1 in mediating DUXAP8 phenotypes. Our results showed that DUXAP8 was significantly upregulated in HCC tissues or cell lines associated with tumors of advanced grades, tumors that were positive for lymph node metastasis, and patients with poor overall survival. DUAXP8 was essential in maintaining multiple malignant phenotypes (including resistance to olaparib) both in vitro and in vivo. Mechanistically, DUXAP8 upregulated FOXM1 expression by sponging miR-485-5p and interacting with the RNA-binding protein Fused in Sarcoma (FUS). Functionally, FOXM1 essentially mediated the oncogenic phenotypes of DUXAP8. Collectively, DUXAP8 acts through two distinct mechanisms to upregulate FOXM1 and becomes a pleotropic oncogenic lncRNA in HCC.http://www.sciencedirect.com/science/article/pii/S2372770520301613hepatocellular carcinomaDUXAP8miR-485-5pFOXM1PARP inhibitor |
| spellingShingle | Yu Hu Xian Zhang Hong-Yan Zai Wei Jiang Liang Xiao Qin Zhu lncRNA DUXAP8 Facilitates Multiple Malignant Phenotypes and Resistance to PARP Inhibitor in HCC via Upregulating FOXM1 Molecular Therapy: Oncolytics hepatocellular carcinoma DUXAP8 miR-485-5p FOXM1 PARP inhibitor |
| title | lncRNA DUXAP8 Facilitates Multiple Malignant Phenotypes and Resistance to PARP Inhibitor in HCC via Upregulating FOXM1 |
| title_full | lncRNA DUXAP8 Facilitates Multiple Malignant Phenotypes and Resistance to PARP Inhibitor in HCC via Upregulating FOXM1 |
| title_fullStr | lncRNA DUXAP8 Facilitates Multiple Malignant Phenotypes and Resistance to PARP Inhibitor in HCC via Upregulating FOXM1 |
| title_full_unstemmed | lncRNA DUXAP8 Facilitates Multiple Malignant Phenotypes and Resistance to PARP Inhibitor in HCC via Upregulating FOXM1 |
| title_short | lncRNA DUXAP8 Facilitates Multiple Malignant Phenotypes and Resistance to PARP Inhibitor in HCC via Upregulating FOXM1 |
| title_sort | lncrna duxap8 facilitates multiple malignant phenotypes and resistance to parp inhibitor in hcc via upregulating foxm1 |
| topic | hepatocellular carcinoma DUXAP8 miR-485-5p FOXM1 PARP inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S2372770520301613 |
| work_keys_str_mv | AT yuhu lncrnaduxap8facilitatesmultiplemalignantphenotypesandresistancetoparpinhibitorinhccviaupregulatingfoxm1 AT xianzhang lncrnaduxap8facilitatesmultiplemalignantphenotypesandresistancetoparpinhibitorinhccviaupregulatingfoxm1 AT hongyanzai lncrnaduxap8facilitatesmultiplemalignantphenotypesandresistancetoparpinhibitorinhccviaupregulatingfoxm1 AT weijiang lncrnaduxap8facilitatesmultiplemalignantphenotypesandresistancetoparpinhibitorinhccviaupregulatingfoxm1 AT liangxiao lncrnaduxap8facilitatesmultiplemalignantphenotypesandresistancetoparpinhibitorinhccviaupregulatingfoxm1 AT qinzhu lncrnaduxap8facilitatesmultiplemalignantphenotypesandresistancetoparpinhibitorinhccviaupregulatingfoxm1 |