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Long noncoding RNA LINC00673 epigenetically suppresses KLF4 by interacting with EZH2 and DNMT1 in gastric cancer
Ming-Chen Ba1, Hui Long2, Shu-Zhong Cui1
1Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, P.R. China.
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.
Insights
Long non-coding RNA LINC00673 is highly expressed in gastric cancer (GC) and linked to poor prognosis. Inhibiting LINC00673 suppressed GC cell growth and invasion, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
- The specific function of LINC00673 in gastric cancer (GC) progression remains largely undefined.
Purpose of the Study:
- To investigate the role and clinical significance of LINC00673 in gastric cancer.
- To explore the underlying molecular mechanisms of LINC00673 in GC development.
Main Methods:
- Quantitative analysis of LINC00673 expression in GC tissues versus normal tissues.
- Correlation analysis between LINC00673 levels and clinical parameters (metastasis, TNM stage, survival).
- In vitro experiments involving LINC00673 knockdown in GC cells, including proliferation, migration, and invasion assays.
- RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays to elucidate molecular interactions.
Main Results:
- LINC00673 expression was significantly upregulated in GC tissues and correlated with lymph node metastasis, distant metastasis, and advanced TNM stage.
- High LINC00673 expression was associated with shorter disease-free survival (DFS) and overall survival (OS), identified as an independent prognostic risk factor.
- Knockdown of LINC00673 inhibited GC cell proliferation, colony formation, migration, and invasion, reducing PCNA, CyclinD1, and CDK2 expression.
- LINC00673 was found to suppress KLF4 expression by interacting with EZH2 and DNMT1, thereby promoting GC cell proliferation and invasion.
Conclusions:
- LINC00673 serves as a potential prognostic biomarker for gastric cancer.
- LINC00673 plays a crucial role in promoting GC progression by repressing KLF4.
- LINC00673 represents a promising therapeutic target for gastric cancer treatment.
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