Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignancies worldwide. Studies seeking to advance the overall understanding of lncRNA profiling in HCC remain rare. Methods The transcriptomic profiling of 12 HCC tissues and paired adjacent normal tissue...

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Main Authors: Jian Yao, Lingjiao Wu, Xiaohua Meng, Huanxia Yang, Shujun Ni, Qiangfeng Wang, Jiawei Zhou, Qiong Zhang, Kunkai Su, Li Shao, Qingyi Cao, Mingding Li, Fusheng Wu, Lanjuan Li
Format: Article
Language:English
Published: BMC 2017-10-01
Series:Molecular Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12943-017-0733-5
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author Jian Yao
Lingjiao Wu
Xiaohua Meng
Huanxia Yang
Shujun Ni
Qiangfeng Wang
Jiawei Zhou
Qiong Zhang
Kunkai Su
Li Shao
Qingyi Cao
Mingding Li
Fusheng Wu
Lanjuan Li
author_facet Jian Yao
Lingjiao Wu
Xiaohua Meng
Huanxia Yang
Shujun Ni
Qiangfeng Wang
Jiawei Zhou
Qiong Zhang
Kunkai Su
Li Shao
Qingyi Cao
Mingding Li
Fusheng Wu
Lanjuan Li
author_sort Jian Yao
collection DOAJ
description Abstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignancies worldwide. Studies seeking to advance the overall understanding of lncRNA profiling in HCC remain rare. Methods The transcriptomic profiling of 12 HCC tissues and paired adjacent normal tissues was determined using high-throughput RNA sequencing. Fifty differentially expressed mRNAs (DEGs) and lncRNAs (DELs) were validated in 21 paired HCC tissues via quantitative real-time PCR. The correlation between the expression of DELs and various clinicopathological characteristics was analyzed using Student’s t-test or linear regression. Co-expression networks between DEGs and DELs were constructed through Pearson correlation co-efficient and enrichment analysis. Validation of DELs’ functions including proliferation and migration was performed via loss-of-function RNAi assays. Results In this study, we identified 439 DEGs and 214 DELs, respectively, in HCC. Furthermore, we revealed that multiple DELs, including NONHSAT003823, NONHSAT056213, NONHSAT015386 and especially NONHSAT122051, were remarkably correlated with tumor cell differentiation, portal vein tumor thrombosis, and serum or tissue alpha fetoprotein levels. In addition, the co-expression network analysis between DEGs and DELs showed that DELs were involved with metabolic, cell cycle, chemical carcinogenesis, and complement and coagulation cascade-related pathways. The silencing of the endogenous level of NONHSAT122051 or NONHSAT003826 could significantly attenuate the mobility of both SK-HEP-1 and SMMC-7721 HCC cells. Conclusion These findings not only add knowledge to the understanding of genome-wide transcriptional evaluation of HCC but also provide promising targets for the future diagnosis and treatment of HCC.
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spelling doaj.art-331b08e890da4e26a6531a864ddd538f2022-12-21T21:14:43ZengBMCMolecular Cancer1476-45982017-10-0116111010.1186/s12943-017-0733-5Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinomaJian Yao0Lingjiao Wu1Xiaohua Meng2Huanxia Yang3Shujun Ni4Qiangfeng Wang5Jiawei Zhou6Qiong Zhang7Kunkai Su8Li Shao9Qingyi Cao10Mingding Li11Fusheng Wu12Lanjuan Li13State Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Ultrasonography, The Women’s Hospital, School of Medicine, Zhejiang UniversityState Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Medical Oncology, Cancer Center, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityDepartment of Surgical Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang UniversityState Key Laboratory for Dianosis and Treatment of Infectious Diseases, Collaborate Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityAbstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignancies worldwide. Studies seeking to advance the overall understanding of lncRNA profiling in HCC remain rare. Methods The transcriptomic profiling of 12 HCC tissues and paired adjacent normal tissues was determined using high-throughput RNA sequencing. Fifty differentially expressed mRNAs (DEGs) and lncRNAs (DELs) were validated in 21 paired HCC tissues via quantitative real-time PCR. The correlation between the expression of DELs and various clinicopathological characteristics was analyzed using Student’s t-test or linear regression. Co-expression networks between DEGs and DELs were constructed through Pearson correlation co-efficient and enrichment analysis. Validation of DELs’ functions including proliferation and migration was performed via loss-of-function RNAi assays. Results In this study, we identified 439 DEGs and 214 DELs, respectively, in HCC. Furthermore, we revealed that multiple DELs, including NONHSAT003823, NONHSAT056213, NONHSAT015386 and especially NONHSAT122051, were remarkably correlated with tumor cell differentiation, portal vein tumor thrombosis, and serum or tissue alpha fetoprotein levels. In addition, the co-expression network analysis between DEGs and DELs showed that DELs were involved with metabolic, cell cycle, chemical carcinogenesis, and complement and coagulation cascade-related pathways. The silencing of the endogenous level of NONHSAT122051 or NONHSAT003826 could significantly attenuate the mobility of both SK-HEP-1 and SMMC-7721 HCC cells. Conclusion These findings not only add knowledge to the understanding of genome-wide transcriptional evaluation of HCC but also provide promising targets for the future diagnosis and treatment of HCC.http://link.springer.com/article/10.1186/s12943-017-0733-5Hepatocellular carcinomaLong non-coding RNARNA sequencingCo-expression networkCell migration
spellingShingle Jian Yao
Lingjiao Wu
Xiaohua Meng
Huanxia Yang
Shujun Ni
Qiangfeng Wang
Jiawei Zhou
Qiong Zhang
Kunkai Su
Li Shao
Qingyi Cao
Mingding Li
Fusheng Wu
Lanjuan Li
Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma
Molecular Cancer
Hepatocellular carcinoma
Long non-coding RNA
RNA sequencing
Co-expression network
Cell migration
title Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma
title_full Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma
title_fullStr Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma
title_full_unstemmed Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma
title_short Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma
title_sort profiling clinicopathological correlation and functional validation of specific long non coding rnas for hepatocellular carcinoma
topic Hepatocellular carcinoma
Long non-coding RNA
RNA sequencing
Co-expression network
Cell migration
url http://link.springer.com/article/10.1186/s12943-017-0733-5
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