Lingzhi Peng1*, Tianxiang Liu1*, Chenglou Zhu2*, Chongya Yang3, Qiong Wang4, Mingxu Da1,2
1Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou, 730000, China.
2First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China.
3Department of Geriatrics, Lintao County Hospital of Chinese Medicine, Dingxi, 730500, China.
4Department of Internal Medicine, Second People’s Hospital of Jiuquan City, Jiuquan, 735000, China.
*These authors contributed equally to this work.
Summary
Purpose: Long non-coding RNAs (lncRNAs) promote gastric cancer invasion and metastasis via epithelial-to-mesenchymal transition (EMT). Super enhancers (SEs) regulate the expression of key oncogenic lncRNAs. Here, we attempted to identify EMT-regulating SE-associated lncRNAs.
Methods: H3K27ac histone acetylation was used as an SE marker, and chromatin immunoprecipitation sequencing (ChIP-seq) was performed to compare the SE landscape in SGC-7901 gastric adenocarcinoma and GES-1 in non-cancer gastric mucosa cell lines. Cancer associated transcript-1 (CCAT1) was knocked down in MKN-45 gastric adenocarcinoma cells and overexpressed in SGC-7901 cells. CCAT1 was detected by real-time PCR in GES-1, SGC-7901, and MKN-45 cells. Cell proliferation, migration and invasion were analyzed by Cell Counting kit-8, wound healing, and transwell assays, respectively. E-cadherin and N-cadherin expression was evaluated by western blotting.
Results: We identified 838 SEs in SGC-7901 and 206 SEs in GES-1 cells. SE-associated CCAT1 was identified as an EMT-related lncRNA upregulated in SGC-7901 and MKN45 cells. Analysis of the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas revealed elevated CCAT1 expression in various tumor cells and tissues. CCAT1 expression was associated with high cell proliferation, invasion, and migration and correlated negatively with E-cadherin, but positively with N-cadherin levels.
Conclusions: CCAT1 is upregulated in gastric cancer cells. CCAT1 is an EMT-promoting and SE-associated lncRNA that promotes cell proliferation, invasion, and migration. Therefore, CCAT1 may represent a potential diagnostic and therapeutic target for gastric cancer.
Key words: colon cancer associated transcript-1, epithelial-to-mesenchymal transition, gastric cancer, long non-coding RNA, super enhancer.
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