HoxC6 Functions as an Oncogene and Isoform HoxC6-2 May Play the Primary Role in Gastric Carcinogenesis
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ORIGINAL ARTICLE
HoxC6 Functions as an Oncogene and Isoform HoxC6‑2 May Play the Primary Role in Gastric Carcinogenesis Jinping Lin1 · Jiamin He1,2 · Xingkang He1,2 · Lan Wang1,2 · Meng Xue2 · Wei Zhuo2 · Jianmin Si1,2 · Kan Wang1,2 · Shujie Chen1,2 Received: 9 August 2018 / Accepted: 12 December 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Based on previous researches of HoxC6, this study aims to investigate the expression levels of isoforms HoxC6-1 and HoxC6-2 and to explore their roles in gastric carcinogenesis as well as the possible molecular mechanism. Methods We investigated expression levels of HoxC6, HoxC6-1, and HoxC6-2 in gastric cancer tissues, coupled with relevant data in TCGA dataset. In vitro, HoxC6, HoxC6-1, and HoxC6-2 knockdown by small interference RNA was carried for evaluating the changes of malignant biological behaviors of gastric cancer cells, such as proliferation, migration, invasion, apoptosis, and cell cycle alternation. Metastasis-related nucleotide lncRNA HOTAIR was selected by bioinformatics, and verification was carried out by in vitro researches. Results Data suggested HoxC6-1 and HoxC6-2 were considerably over-expressed with different folds in gastric cancerous tissues. Decreased expression of HoxC6-2 was detected in well-differentiated type of gastric cancer. In vitro, the conclusion that HoxC6 functions as a tumor oncogene illuminated by previous studies was verified again. Additionally, down-regulating of HoxC6-2 significantly inhibited SGC-7901 and BGC-823 cells from proliferation, migration, invasion, apoptosis, while quite slight results or none statistically significant results were observed when HoxC6-1 was knockdown. Besides, over-expression of HOTAIR, which is relevant with HoxC6 during gastric carcinogenesis, was detected in gastric cancerous tissues. Restored expression of HoxC6 partially reversed the decreased migration caused by down-regulating HOTAIR in gastric cancer cells. Conclusion HoxC6 acts as an oncogene in gastric carcinogenesis and might be a promising therapeutic target. Isoform HoxC6-2 plays a primary carcinogenic role in gastric carcinogenesis. HOTAIR, over-expressed in gastric cancer, might regulate HoxC6 on the protein level in promoting migration of gastric cells. Keywords Gastric cancer · HoxC6 · Isoform · Biological behaviors · lncRNA HOTAIR
Introduction Jinping Lin and Jiamin He have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10620-019-06013-7) contains supplementary material, which is available to authorized users. * Shujie Chen [email protected] 1
Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, #3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, People’s Republic of China
Institute of Gastroenterology, Zhejiang University, #3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, People’s Republic of China
2
Gastric cancer is one
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