Retrospective Study
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World J Gastroenterol. Aug 28, 2014; 20(32): 11347-11355
Published online Aug 28, 2014. doi: 10.3748/wjg.v20.i32.11347
MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin
Xiang-Liang Zhang, Hui-Juan Shi, Ji-Ping Wang, Hong-Sheng Tang, Yin-Bing Wu, Zhi-Yuan Fang, Shu-Zhong Cui, Lian-Tang Wang
Xiang-Liang Zhang, Hong-Sheng Tang, Yin-Bing Wu, Zhi-Yuan Fang, Shu-Zhong Cui, Department of Abdominal Surgery (Section 2), Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou 510095, Guangdong Province, China
Hui-Juan Shi, Lian-Tang Wang, Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Ji-Ping Wang, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States
Author contributions: Zhang XL and Shi HJ contributed equally to this work; Cui SZ and Wang LT supervised the experiment; Zhang XL and Fang ZY wrote and revised the paper; all authors read and approved the final manuscript.
Supported by The PhD Start-up Funds of Guangzhou Medical College, Guangdong Province, China, No. 2012C66 and No. 2012C69; Guangdong Province Natural Science Fund, No. S2013010016662; and the National Natural Science Foundation of China, No. 81201932 and No. 81372493
Correspondence to: Lian-Tang Wang, Professor, Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China. wanglt@mail.sysu.edu.cn
Telephone: +86-20-87331780 Fax: +86-20-87331780
Received: January 5, 2014
Revised: April 9, 2014
Accepted: May 19, 2014
Published online: August 28, 2014
Processing time: 236 Days and 11.2 Hours
Abstract

AIM: To investigate the molecular mechanisms of miRNA in advanced gastric cancers (AGCs) before and after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC).

METHODS: A miRNA microarray containing human mature and precursor miRNA sequences was used to compare expression profiles in serum samples of 5 patients with AGC before and after CRS + HIPEC. The upregulation of miR-218 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in SGC7901 gastric cancer cells.

RESULTS: miRNA microarray chip analysis found that the level of miR-218 expression was upregulated more than 8 fold after CRS + HIPEC. Furthermore, miR-218 increased gastric cancer cell chemosensitivity to cisplatin in vitro and inhibited gastric cell tumor growth in nude mice in vivo (0.5 vs 0.78, P < 0.05).

CONCLUSION: Our results indicated that targeting miR-218 may provide a strategy for blocking the development of gastric cancer and reverse the multi-drug resistance of gastric cell lines.

Keywords: Advanced gastric cancer; Cytoreductive surgery; Hyperthermic intraperitoneal chemotherapy; miR-218; Multi-drug resistance; MicroRNA

Core tip: MicroRNAs (miRNAs) are short single-stranded RNAs associated with gene regulation at the transcriptional and translational levels. miRNA up- or down regulation has been linked to cancer development. We analyzed miRNA expression in advanced gastric cancers before and after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to gain further understanding of the molecular mechanisms of CRS + HIPEC. Furthermore, we described the regulation and function of miR-218 in gastric cancer emphatically. Our results indicated that targeting miR-218 may provide a strategy for blocking the development of gastric cancer and can reverse the multi-drug resistance of gastric cell lines.