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Long non-coding RNA 91H contributes to the occurrence and progression of esophageal squamous cell carcinoma by
Tianyi Gao1, Bangshun He, Yuqin Pan
1Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Abstract:
Long non-coding RNAs (lncRNAs) have been recently recognized as a major class of regulators in mammalian systems. 91H, a novel long noncoding antisense transcripts located on the position of the H19/IGF2 locus has been suggested to play a potential tumor-suppressor role in tumor development. However, little study has proved the mechanism in esophageal squamous cell carcinoma (ESCC). We carried out this study to explore the role of lncRNA 91H in the regulation of H19 imprinting control regions (ICR) and IGF2 expression and the association between 91H and ESCC progression. The cell line TE-1, Eca-109, and 232 ESCC patients' matched sets of paraffin-embedded adjacent normal and tumor samples were obtained in this study. The results showed that 91H expression was significantly lower in patients with higher depth of invasion, neoplastic grading and TNM which usually leads to the overexpression of IGF2 in tumor progression. The expression of 91H usually decreased in TE-1 and Eca-109 when treated with demethylation agent. Further analysis revealed that, in 91H knockdown cell lines, IGF2 expression was also significantly higher than negative controls. Therefore, the results demonstrated that the lncRNA 91H was associated with H19 ICR methylation and inhibited IGF2 expression of ESCC patients which may optimize the mechanism of IGF2 regulation in tumor development. Patients with higher depth of invasion, neoplastic grading and TNM usually demonstrated lower 91H expression potentially represent a novel clinically relevant event to identify individuals at increased risk for the occurrence, progression and prognosis of ESCC.
Insights
Long non-coding RNA 91H acts as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). Lower 91H expression correlates with advanced ESCC, suggesting its role in regulating IGF2 expression and disease progression.
Area of Science:
- Molecular Biology
- Oncology
- Epigenetics
Background:
- Long non-coding RNAs (lncRNAs) are key regulators in biological systems.
- The lncRNA 91H, located at the H19/IGF2 locus, is implicated in tumor suppression.
- Its specific role in esophageal squamous cell carcinoma (ESCC) remains largely unelucidated.
Purpose of the Study:
- To investigate the function of lncRNA 91H in regulating H19 imprinting control regions (ICR) and IGF2 expression.
- To determine the association between 91H expression and ESCC progression.
- To explore the potential of 91H as a biomarker for ESCC risk and prognosis.
Main Methods:
- Analysis of 91H expression in ESCC cell lines (TE-1, Eca-109) and 232 patient tumor samples.
- Treatment of cell lines with a demethylation agent to assess the effect on 91H expression.
- Knockdown of 91H in cell lines to evaluate its impact on IGF2 expression.
- Correlation analysis between 91H expression and clinicopathological features (depth of invasion, grading, TNM stage).
Main Results:
- 91H expression was significantly lower in ESCC patients with advanced disease (higher depth of invasion, neoplastic grading, TNM stage).
- 91H expression decreased in ESCC cell lines upon treatment with a demethylation agent.
- Knockdown of 91H led to a significant increase in IGF2 expression.
- Lower 91H expression was associated with overexpression of IGF2, indicating its inhibitory role.
Conclusions:
- lncRNA 91H is epigenetically regulated and inhibits IGF2 expression in ESCC.
- Reduced 91H expression is linked to ESCC progression and poor prognosis.
- 91H may serve as a novel biomarker for identifying patients at increased risk for ESCC occurrence, progression, and adverse outcomes.
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