Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2
Objective: The long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has emerged as a novel player in hepatocellular carcinoma (HCC). Hypoxia is a common characteristic of the microenvironment of HCC. This study aimed to investigate whether lncRNA-NEAT1 is induced by hypoxia...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00998/full |
| _version_ | 1818309863378255872 |
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| author | Qiangnu Zhang Qiangnu Zhang Qian Cheng Mengting Xia Xiaotao Huang Xiaoyan He Juan Liao |
| author_facet | Qiangnu Zhang Qiangnu Zhang Qian Cheng Mengting Xia Xiaotao Huang Xiaoyan He Juan Liao |
| author_sort | Qiangnu Zhang |
| collection | DOAJ |
| description | Objective: The long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has emerged as a novel player in hepatocellular carcinoma (HCC). Hypoxia is a common characteristic of the microenvironment of HCC. This study aimed to investigate whether lncRNA-NEAT1 is induced by hypoxia in HCC, and the mechanism that underlies LncRNA-NEAT1 function.Methods: The expression changes of lncRNA-NEAT1 in HCC cell lines under hypoxic conditions were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The regulatory effect of HIF-1α on lncRNA-NEAT1 was confirmed with chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The function of lncRNA-NEAT1 on HCC cell growth under hypoxic conditions was determined by CCK-8 assay and flow cytometry. lncRNA -NEAT1 was predicted to serve as a competing endogenous RNA (ceRNA) within microRNA (miRNA)/mRNA axes based on microarray data, public HCC-related datasets and integrative bioinformatics analysis, and the miR-199a-3p/UCK2 axis was selected and validated by qRT-PCR, western blotting, RNA immunoprecipitation, and luciferase reporter analyses. The role of miR-199a-3p/UCK2 in HCC and its functional association with lncRNA-NEAT1 were assessed both in vitro and in vivo.Results: LncRNA-NEAT1 expression was significantly induced by hypoxia in SNU-182 and HUH7 cells. HIF-1α was shown to regulate lncRNA-NEAT1 transcription. Under hypoxic conditions, lncRNA-NEAT1 maintained the growth of HCC cells and inhibited apoptosis and cell cycle arrest. LncRNA-NEAT1 was predicted to regulate a panel of HCC-associated miRNA-mRNA pairs consisting of 8 miRNAs and 13 mRNAs. LncRNA-NEAT1 was shown to function as a ceRNA of miR-199a-3p/UCK2 both in HCC cells under hypoxic conditions and in an animal model.Conclusion: LncRNA-NEAT1 is a hypoxia-responsive lncRNA in HCC cell lines Insilico evidence suggested that LncRNA-NEAT1 may sustainthe growth of HCC cells by regulating HCC-associated mRNAs that interact with tumor-suppressive miRNAs. The lncRNA-NEAT1/miR-199a-3p/UCK2 pathway may contribute to the progression of HCC cell lines in a hypoxic microenvironment and therefore may represent a novel therapeutic target for HCC. |
| first_indexed | 2024-12-13T07:36:55Z |
| format | Article |
| id | doaj.art-1329f3da7017438bbe1955289516f084 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-13T07:36:55Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1329f3da7017438bbe1955289516f0842022-12-21T23:55:03ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-06-011010.3389/fonc.2020.00998543725Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2Qiangnu Zhang0Qiangnu Zhang1Qian Cheng2Mengting Xia3Xiaotao Huang4Xiaoyan He5Juan Liao6Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Guangzhou, ChinaIntegrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, ChinaDepartment of Gastroenterology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaNorth Sichuan Medical College, Nanchong, ChinaNorth Sichuan Medical College, Nanchong, ChinaDepartment of Pathology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaObjective: The long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has emerged as a novel player in hepatocellular carcinoma (HCC). Hypoxia is a common characteristic of the microenvironment of HCC. This study aimed to investigate whether lncRNA-NEAT1 is induced by hypoxia in HCC, and the mechanism that underlies LncRNA-NEAT1 function.Methods: The expression changes of lncRNA-NEAT1 in HCC cell lines under hypoxic conditions were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The regulatory effect of HIF-1α on lncRNA-NEAT1 was confirmed with chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The function of lncRNA-NEAT1 on HCC cell growth under hypoxic conditions was determined by CCK-8 assay and flow cytometry. lncRNA -NEAT1 was predicted to serve as a competing endogenous RNA (ceRNA) within microRNA (miRNA)/mRNA axes based on microarray data, public HCC-related datasets and integrative bioinformatics analysis, and the miR-199a-3p/UCK2 axis was selected and validated by qRT-PCR, western blotting, RNA immunoprecipitation, and luciferase reporter analyses. The role of miR-199a-3p/UCK2 in HCC and its functional association with lncRNA-NEAT1 were assessed both in vitro and in vivo.Results: LncRNA-NEAT1 expression was significantly induced by hypoxia in SNU-182 and HUH7 cells. HIF-1α was shown to regulate lncRNA-NEAT1 transcription. Under hypoxic conditions, lncRNA-NEAT1 maintained the growth of HCC cells and inhibited apoptosis and cell cycle arrest. LncRNA-NEAT1 was predicted to regulate a panel of HCC-associated miRNA-mRNA pairs consisting of 8 miRNAs and 13 mRNAs. LncRNA-NEAT1 was shown to function as a ceRNA of miR-199a-3p/UCK2 both in HCC cells under hypoxic conditions and in an animal model.Conclusion: LncRNA-NEAT1 is a hypoxia-responsive lncRNA in HCC cell lines Insilico evidence suggested that LncRNA-NEAT1 may sustainthe growth of HCC cells by regulating HCC-associated mRNAs that interact with tumor-suppressive miRNAs. The lncRNA-NEAT1/miR-199a-3p/UCK2 pathway may contribute to the progression of HCC cell lines in a hypoxic microenvironment and therefore may represent a novel therapeutic target for HCC.https://www.frontiersin.org/article/10.3389/fonc.2020.00998/fullhepatocellular carcinomaLncRNA-NEAT1microRNAUCK2hypoxia |
| spellingShingle | Qiangnu Zhang Qiangnu Zhang Qian Cheng Mengting Xia Xiaotao Huang Xiaoyan He Juan Liao Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2 Frontiers in Oncology hepatocellular carcinoma LncRNA-NEAT1 microRNA UCK2 hypoxia |
| title | Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2 |
| title_full | Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2 |
| title_fullStr | Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2 |
| title_full_unstemmed | Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2 |
| title_short | Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2 |
| title_sort | hypoxia induced lncrna neat1 sustains the growth of hepatocellular carcinoma via regulation of mir 199a 3p uck2 |
| topic | hepatocellular carcinoma LncRNA-NEAT1 microRNA UCK2 hypoxia |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00998/full |
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