Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2016; 22(32): 7322-7331
Published online Aug 28, 2016. doi: 10.3748/wjg.v22.i32.7322
Protein and gene expression characteristics of heterogeneous nuclear ribonucleoprotein H1 in esophageal squamous cell carcinoma
Yu-Lin Sun, Fei Liu, Fang Liu, Xiao-Hang Zhao
Yu-Lin Sun, Fei Liu, Fang Liu, Xiao-Hang Zhao, State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Author contributions: Sun YL and Zhao XH designed the study; Sun YL, Liu F and Liu F performed the research; Sun YL analyzed the data and wrote the manuscript; Zhao XH supervised this work.
Supported by the Natural Science Foundation of China, No. 81572840, No. 81372591 and No. 81572365; the State Key Project for Basic Research, No. 2014CBA02002; and National High-tech R and D Program, No. 2012AA020206.
Institutional review board statement: All routine clinic biopsy specimens and blood samples from the patients were taken after informed consent and ethical permission was obtained for participation in the study.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: Technical appendix and dataset available from the corresponding author. Participants gave informed consent for data sharing. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xiao-Hang Zhao, MD, PhD, Professor, State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17, Chaoyang District, Beijing 100021, China. zhaoxh@cicams.ac.cn
Telephone: +86-10-67709015 Fax: +86-10-87778360
Received: March 26, 2016
Peer-review started: March 28, 2016
First decision: May 12, 2016
Revised: May 16, 2016
Accepted: June 2, 2016
Article in press: June 2, 2016
Published online: August 28, 2016
Abstract
AIM

To investigate the expression characteristics of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) mRNA and protein in cell lines and tissues of esophageal squamous cell carcinoma (ESCC).

METHODS

Western blotting was used to assess the expression of HNRNPH1 protein in seven ESCC cell lines and 30 paired fresh tissue specimens. The subcellular localization of HNRNPH1 was determined by immunofluorescence in ESCC cells. The RNA sequencing data from 87 patients with ESCC were obtained from the cancer genome atlas (TCGA), and the expression and clinical characteristics analysis of different transcript variants of HNRNPH1 were evaluated in this dataset. In addition, immunohistochemistry was carried out to detect the expression of HNRNPH1 protein in 125 patients.

RESULTS

The expression of HNRNPH1 protein varied across different ESCC cell lines. It was exclusively restricted to the nucleus of the ESCC cells. There are two transcript variants of the HNRNPH1 gene. Variant 1 was constitutively expressed, and its expression did not change during tumorigenesis. In contrast, levels of variant 2 were low in non-tumorous tissues and were dramatically increased in ESCC (P = 0.0026). The high levels of variant 2 were associated with poorer differentiated tumors (P = 0.0287). Furthermore, in paired fresh tissue specimens, HNRNPH1 protein was overexpressed in 73.3% (22/30) of neoplastic tissues. HNRNPH1 was significantly upregulated in ESCC, with strong staining in 43.2% (54/125) of tumor tissues and 22.4% (28/125) of matched non-cancerous tissues (P = 0.0005). Positive HNRNPH1 expression was significantly associated with poor tumor differentiation degree (P = 0.0337).

CONCLUSION

The different alternative transcript variants of HNRNPH1 exhibited different expression changes during tumorigenesis. Its mRNA and protein were overexpressed in ESCC and associated with poorer differentiation of tumor cells. These findings highlight the potential of HNRNPH1 in the therapy and diagnosis of ESCC.

Keywords: Heterogeneous nuclear ribonucleoprotein H1, Esophageal squamous cell carcinoma, Alternative transcript variants, Biomarker

Core tip: Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) is an evolutionarily conserved splicing factor. It is involved in alternative splicing, polyadenylation, mRNA export, and translation. This study investigated the expression, localization, and clinical significance of HNRNPH1 in esophageal squamous cell carcinoma (ESCC). We found that this gene possesses two alternative transcript variants; one was constitutively expressed, while the other was regulated and dramatically increased in ESCC. HNRNPH1 protein was overexpressed in ESCC tissues. Strong HNRNPH1 levels were associated with poorer tumor differentiation and alternative splicing of apoptosis-related genes. These findings suggest that HNRNPH1 is a potential diagnostic biomarker and therapeutic target for ESCC.