A cancer-testis non-coding RNA LIN28B-AS1 activates driver gene LIN28B by interacting with IGF2BP1 in lung adenocarcinoma

Our previous work found cancer-testis (CT) genes as a new source of epi-driver candidates of cancer. LIN28B was a CT gene, but the driver ability and the activation mechanism in lung adenocarcinoma (LUAD) remain unclear. We observed that LIN28B expression was restricted in testis. It was re-activated in LUAD patients without known genomic alterations in oncogenes and was related to poorer survival. In vitro and In vivo experiments confirmed that the activation of LIN28B could promote the proliferation and metastasis of LUAD cells and can influence cell cycle, DNA damage repair, and genome instability. In addition to the known let-7-LIN28B regulation loop, our results further revealed a let-7-independent Cis-regulator of LIN28B: LIN28B-ASI. LIN28B-ASI is a CT long non-coding RNA (CT-lncRNA). It altered the messenger RNA stability of LIN28B by directly interacting with another CT protein IGF2BP1 but not with LIN28B and constituted a novel regulation network. In sum, we identify that LIN28B is an epi-driver of LUAD and clarify a new lncRNA-activated mechanism of LIN28B, which provide new candidate targets for precise anticancer therapy in the future.