Abstract
Long non-coding RNAs (lncRNAs), a variety of transcripts without protein coding ability, have recently been reported to play vital roles in gastric cancer (GC) development and progression. However, the biological role of long non-coding RNA LINC00673 in GC is not fully known. In the study, we found that LINC00673 expression was dramatically higher in gastric cancer tissues compared with adjacent normal tissues, and positively associated with lymph node metastasis, distant metastasis and TNM stage in patients. Higher LINC00673 expression predicted poor disease-free survival (DFS) and overall survival (OS) in GC patients. By univariate and multivariate Cox analysis, the results confirmed that higher LINC00673 expression was an independent risk factor of prognosis in patients. Knockdown of endogenous LINC00673 significantly inhibited cell proliferation, colony formation number, cell migration and invasion in GC. Furthermore, knockdown of endogenous LINC00673 reduced the expression levels of PCNA, CyclinD1 and CDK2 in GC cells. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) proved that LINC00673 suppressed KLF4 expression by interacting with EZH2 and DNMT1 in GC cells. Moreover, we confirmed that LINC00673 promoted cell proliferation and invasion by partly repressing KLF4 expression in GC. Taken together, these results indicated that LINC00673 may be a prognostic biomarker and therapeutic target for GC patients.
Highlights
Gastric cancer (GC) is one of the most common types of cancer with high morbidity and mortality worldwide [1]
We investigated the relationship between LINC00673 expression and disease-free survival (DFS) and overall survival (OS) in gastric cancer (GC) patients
Univariate and multivariate Cox model demonstrated that lymph node metastasis, distance metastasis, advanced TNM stage and higher LINC00673 expression were identified as independent risk factors for DFS (Table 2) or OS (Table 3) in patients
Summary
Gastric cancer (GC) is one of the most common types of cancer with high morbidity and mortality worldwide [1]. Recent literatures have reported that long noncoding RNAs (lncRNAs) dysregulated in a variety of tumors and function as critical regulators of cancer progression. Downregulated expression of the long non-coding RNA LINC00261 predicts poor prognosis for gastric cancer patients and suppresses tumor metastasis by regulating the epithelial-mesenchymal transition (EMT) process [4]. Over-expression of long www.impactjournals.com/oncotarget non-coding RNA HOTTIP promotes tumor invasion and predicts a poor prognosis in gastric cancer patients [6]. Over-expression of long non-coding antisense RNA KRT7-AS promotes gastric cancer progression via increasing KRT7 expression level [7]. These studies indicated that lncRNAs are responsible for the progression of GC
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