Long non-coding RNA LINC00628 functions as a gastric cancer suppressor via long-range modulating the expression of cell cycle related genes.
To discover new biomarkers for gastric cancer (GC) diagnose and treatment, we screened the lncRNAs in GC tissues from 5 patients. We found 6 lncRNAs had altered expression, and in the same time, the levels of their neighboring genes (located near 300 kb upstream or downstream of lncRNA locus) were significantly changed. After confirming the results of microarray by qRT-PCR in 82 GC patients, the biological function of LINC00628 was examined through cell proliferation and apoptosis, cell migration and invasion, colony formation assay and cell cycle detection. We confirmed that LINC00628 functions as a GC suppressor through suppressing proliferation, migration and colony formation of cancer cells. Furthermore, LINC00628 can also suppress the tumor size in mouse xenograft models. Although LINC00628 can modulate LRRN2 expression, the GC suppressor function of LINC00628 is not LRRN2 dependent. The result of mRNA microarray indicated that LINC00628 perform GC inhibitor function through long-range modulating cell cycle related genes. Importantly, we confirmed that LINC00628 mainly located in the nucleus and interacted with EZH2, and modulated genes expression by regulating H3K27me3 level. This research shed light on the role of dysregulated LINC00628 during GC process and may serve as a potential target for therapeutic intervention.
Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
Zi-Zhen
ZZ
Zhang
Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
Gang
G
Zhao
Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
Chun
C
Zhuang
Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
Yan-Ying
YY
Shen
Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
Wen-Yi
WY
Zhao
Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
Jia
J
Xu
Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
Ming
M
Wang
Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
Chao-Jie
CJ
Wang
Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
Lin
L
Tu
Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
Hui
H
Cao
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.
Zhi-Gang
ZG
Zhang
D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D049109:Cell Proliferation; D016147:Genes, Tumor Suppressor; D018816:Genes, cdc; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D062085:RNA, Long Noncoding / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D015996:Survival Rate
D015816:Cell Adhesion Molecules, Neuronal; C113373:LRRN2 protein, human; D062085:RNA, Long Noncoding