LINC00862 Inhibits Hepatocellular Carcinoma via a RBM47-mediated Positive Feedback Loop

Hepatocellular carcinoma (HCC) continues to claim a significant number of lives worldwide, yet the molecular drivers behind its progression remain elusive. Despite the annotation of thousands of long non-coding RNAs (lncRNAs) as transcriptional products, their specific roles in suppressing HCC remain poorly understood. Here, we have uncovered LINC00862, a lncRNA that exhibits pronounced downregulation in HCC tissues and whose expression levels linked positively to favorable HCC outcomes, as a function of tumor stage and size. Through in-depth functional assays, we have established the formidable anti-tumor effects of LINC00862 on HCC processes such as proliferation, invasion, metastasis, and growth in both in vitro and in vivo settings. Mechanistically, our detailed RNA sequencing and quantitative proteomics analyses 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 profound tumor-suppressive effects. Furthermore, we discovered the critical role of Hoogsteen pairing in LINC00862's ability to bind to the RBM47 promoter and recruit CHD5 as a transcription factor, promoting RBM47 transcriptional upregulation in HCC cells. It is intriguing to note that we also discovered that RBM47 is able to 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.