Case Control Study
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World J Gastroenterol. Apr 21, 2020; 26(15): 1775-1791
Published online Apr 21, 2020. doi: 10.3748/wjg.v26.i15.1775
Value of long non-coding RNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy
Zhen-Yang Li, Hui-Fen Li, Ying-Ying Zhang, Xue-Lan Zhang, Bing Wang, Jiang-Ting Liu
Zhen-Yang Li, Hui-Fen Li, Ying-Ying Zhang, Xue-Lan Zhang, Jiang-Ting Liu, Department of Scientific Research, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
Bing Wang, Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Liu JT and Li ZY performed the majority of experiments and analyzed the data; Li HF and Zhang YY performed the molecular investigations; Zhang XL and Wang B designed and coordinated the research; Li ZY and Li HF wrote the paper.
Institutional review board statement: This study was reviewed and approved by the Qilu Hospital of Shandong University Ethics Committee.
Informed consent statement: All patients in our study provided informed consent.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Jiang-Ting Liu, PhD, Professor, Department of Scientific Research, Shandong University of Traditional Chinese Medicine, No. 4655, Changqing District, Jinan 250355, Shandong Province, China.
Received: December 11, 2019
Peer-review started: December 11, 2019
First decision: January 13, 2020
Revised: January 23, 2020
Accepted: March 19, 2020
Article in press: March 19, 2020
Published online: April 21, 2020

Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy. Poor responses to radiotherapy in most patients generally result in local radiotherapy failure, so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance. The long non-coding RNA (lncRNA) Rpph1 is highly expressed in human gastric cancer tissues, and represses breast cancer cell proliferation and tumorigenesis. However, the expression of lncRNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.


To explore the value of lncRNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.


Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants. The expression of Rpph1 was determined by qRT-PCR. siRNA-NC and siRNA-Rpph1 were transfected into esophageal cancer cell lines, and cells without transfection were designated as the blank control group. Cell survival was tested by colony formation assays, and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays. Cell proliferation was assessed by MTT assays, cell apoptosis by flow cytometry, and cell migration by wound-healing assays. Changes in cell cycle distribution were monitored.


Rpph1 was highly expressed in esophageal carcinoma, making it a promising marker for the diagnosis of esophageal cancer. Rpph1 could also be used to distinguish different short-term responses, T stages, N stages, and clinical stages of esophageal cancer patients. The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression (P < 0.05). In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy, stronger apoptosis in esophageal cancer cells induced by radiotherapy, higher expression of Bax and caspase-3, and lower expression of Bcl-2 (Bax, caspase-3, and Bcl-2 are apoptosis-related proteins). Additionally, silencing Rpph1 attenuated radiation-induced G2/M phase arrest, and significantly inhibited the expression of proteins involved in cell proliferation, migration, and epithelial-mesenchymal transition regulation in esophageal cancer cells.


Rpph1 is highly expressed in esophageal cancer. Silencing Rpph1 expression can promote cell apoptosis, inhibit cell proliferation and migration, and increase radio-sensitivity.

Keywords: Long non-coding RNA Rpph1, Esophageal cancer, Cell sensitivity to radiotherapy, Apoptosis, Cell cycle, Epithelial-mesenchymal transition

Core tip: This study investigated the clinical value of the long non-coding RNA Rpph1 in esophageal cancer, and analyzed the relationship between Rpph1 and the pathological parameters and prognosis of esophageal cancer. We also studied the effect of Rpph1 on the sensitivity of esophageal cancer to radiotherapy, on cell apoptosis, proliferation, migration, and cell cycle, as well as its effect on epithelial-mesenchymal transition-related proteins.