LncRNA HAND2-AS1 controls liver cancer stem cell functions and serves as a potential therapy target (RNA microarray)

Investigation the RNA profiling in Huh7 cells upon knock-out lncRNA HAND2-AS1 or knock-down INO80 via gene expression microarray analysis Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal and maintenance are poorly understood. Here we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs. Human HAND2-AS1 is highly conserved to its mouse ortholog lncHand2. HAND2-AS1 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanically, HAND2-AS1 recruits the INO80 complex onto BMPR1A promoter to trigger its expression, leading to the activation of BMP signaling. Importantly, targeting HAND2-AS1 by antisense oligonucleotides (ASOs) and BMPR1A by siRNAs have synergistic anti-tumor effects on humanized HCC models. Moreover, knockout of lncHand2 or Bmpr1a in mouse hepatocytes impairs BMP signaling and suppresses the initiation of liver cancer. Our findings reveal that HAND2-AS1 promotes the self-renewal of liver CSCs and drives liver oncogenesis, which may be a potential target for HCC therapy. Two-color expression assay for HAND2-AS1 KO vs scr and INO80 KD vs scr.