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.
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