The role of positive feedback loop between LINC00862 and RBM47 in hepatocellular carcinoma suppression
Tao Guo1, Yingying Jiang2, Shunshun Zhu1
1Department of Pathophysiology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, China.
Abstract:
While the dynamic interaction between long non-coding RNA (lncRNA) and RNA binding proteins is widely recognized as pivotal in the regulation of hepatocellular carcinoma (HCC), the precise underlying mechanisms and networks governing their effects remain elusive. Here, we have uncovered LINC00862, a novel lncRNA that exhibits pronounced down-regulation in HCC tissues and whose expression levels are linked positively to favorable HCC outcomes, as a function of tumor stage and size. Through functional assays, we have established the anti-tumor effects of LINC00862 on HCC processes such as proliferation, invasion, metastasis, and growth in vitro and in vivo. Mechanistically, RNA sequencing and quantitative proteomics analyses have revealed that LINC00862's downstream target effector in HCC cells is RBM47. Our further experimentation strongly supports RBM47 as a central mediator of LINC00862's tumor-suppressive effects. Furthermore, our study elucidates the ability of LINC00862 to engage in Hoogsteen pairing interaction with the RBM47 promoter, while simultaneously recruiting the transcription factor CHD5 to elicit RBM47 transcriptional activation, ultimately resulting in transcriptional up-regulation and its consequential expression in hepatoma cells. It is intriguing to note that we also discovered that RBM47 could act as a transcription factor, positively regulating LINC00862 expression. Our identification of a positive feedback loop involving LINC00862 and RBM47 expands our comprehension of the intricate regulatory network that shapes HCC pathogenesis. LINC00862 represents a promising molecular marker for HCC diagnosis and therapeutics.
Insights
A newly discovered long non-coding RNA (lncRNA), LINC00862, shows reduced levels in liver cancer (HCC) and suppresses tumor growth. It works with RBM47, forming a feedback loop that could be key for HCC diagnosis and treatment.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- The interaction between long non-coding RNAs (lncRNAs) and RNA-binding proteins is crucial for hepatocellular carcinoma (HCC) regulation.
- Precise mechanisms and regulatory networks involving lncRNAs in HCC remain largely unknown.
Purpose of the Study:
- To identify and characterize novel lncRNAs involved in HCC pathogenesis.
- To elucidate the functional role and molecular mechanism of LINC00862 in HCC.
- To explore the potential of LINC00862 as a diagnostic marker and therapeutic target for HCC.
Main Methods:
- Analysis of LINC00862 expression in HCC tissues and correlation with clinical outcomes.
- Functional assays (in vitro and in vivo) to assess the anti-tumor effects of LINC00862.
- RNA sequencing, quantitative proteomics, and molecular experiments to identify downstream targets and regulatory mechanisms.
Main Results:
- LINC00862 is significantly down-regulated in HCC tissues and associated with better patient outcomes.
- LINC00862 exhibits potent anti-tumor activities, inhibiting HCC cell proliferation, invasion, metastasis, and growth.
- LINC00862 directly interacts with RBM47, recruiting CHD5 to activate RBM47 transcription; RBM47 reciprocally enhances LINC00862 expression, forming a positive feedback loop.
Conclusions:
- LINC00862 acts as a tumor suppressor in HCC by regulating RBM47.
- The identified positive feedback loop between LINC00862 and RBM47 provides new insights into HCC regulatory networks.
- LINC00862 is a promising biomarker for HCC diagnosis and a potential therapeutic target.
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