LOC401317, a p53-regulated long non-coding RNA, inhibits cell proliferation and induces apoptosis in the nasopharyngeal carcinoma cell line HNE2

Zhaojian Gong; Shanshan Zhang; Zhaoyang Zeng; Hanjiang Wu; Qian Yang; Fang Xiong; Lei Shi; Jianbo Yang; Wenling Zhang; Yanhong Zhou; Yong Zeng; Xiayu Li; Bo Xiang; Shuping Peng; Ming Zhou; Xiaoling Li; Ming Tan; Yong Li; Wei Xiong; Guiyuan Li

doi:10.1371/journal.pone.0110674

LOC401317, a p53-regulated long non-coding RNA, inhibits cell proliferation and induces apoptosis in the nasopharyngeal carcinoma cell line HNE2

PLoS One. 2014 Nov 25;9(11):e110674. doi: 10.1371/journal.pone.0110674. eCollection 2014.

Authors

Zhaojian Gong¹, Shanshan Zhang², Zhaoyang Zeng³, Hanjiang Wu⁴, Qian Yang⁵, Fang Xiong⁶, Lei Shi⁷, Jianbo Yang⁸, Wenling Zhang⁹, Yanhong Zhou¹⁰, Yong Zeng¹¹, Xiayu Li¹², Bo Xiang¹⁰, Shuping Peng¹⁰, Ming Zhou¹⁰, Xiaoling Li¹⁰, Ming Tan⁹, Yong Li¹³, Wei Xiong³, Guiyuan Li³

Affiliations

¹ Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁵ Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
⁶ Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁷ Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁸ Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Department of Laboratory Medicine and Pathology and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America.
⁹ Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, United States of America.
¹⁰ Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
¹¹ Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
¹² Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
¹³ Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.

Abstract

Recent studies have revealed that long non-coding RNAs participate in all steps of cancer initiation and progression by regulating protein-coding genes at the epigenetic, transcriptional, and post-transcriptional levels. Long non-coding RNAs are in turn regulated by other genes, forming a complex regulatory network. The regulation networks between the p53 tumor suppressor and these RNAs in nasopharyngeal carcinoma remains unclear. The aims of this study were to investigate the regulatory roles of the TP53 gene in regulating long non-coding RNA expression profiles and to study the function of a TP53-regulated long non-coding RNA (LOC401317) in the nasopharyngeal carcinoma cell line HNE2. Long non-coding RNA expression profiling indicated that 133 long non-coding RNAs were upregulated in the human NPC cell line HNE2 cells following TP53 overexpression, while 1057 were downregulated. Among these aberrantly expressed long non-coding RNAs, LOC401317 was the most significantly upregulated one. Further studies indicated that LOC401317 is directly regulated by p53 and that ectopic expression of LOC401317 inhibits HNE2 cell proliferation in vitro and in vivo by inducing cell cycle arrest and apoptosis. LOC401317 inhibited cell cycle progression by increasing p21 expression and decreasing cyclin D1 and cyclin E1 expression and promoted apoptosis through the induction of poly(ADP-ribose) polymerase and caspase-3 cleavage. Collectively, these results suggest that LOC401317 is directly regulated by p53 and exerts antitumor effects in HNE2 nasopharyngeal carcinoma cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis*
Carcinoma
Cell Line, Tumor
Cell Proliferation*
Cyclin D1 / metabolism
Gene Expression Regulation, Neoplastic
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms / genetics
Nasopharyngeal Neoplasms / metabolism*
Nasopharyngeal Neoplasms / pathology
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
Up-Regulation

Substances

RNA, Long Noncoding
Tumor Suppressor Protein p53
Cyclin D1

Associated data

GEO/GSE60379

Grants and funding

This work was supported by grants from The National Natural Science Foundation of China (81171930, 81172189, 81101509, 81272298, 81372907 and 81301757), the Natural Science Foundation of Hunan Province (14JJ1010), and the Research Fund for the Doctoral Program of Higher Education (20130162120083). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.