LncSIK1 enhanced the sensitivity of AML cells to retinoic acid by the E2F1/autophagy pathway.

Ke Wang, Jun-da Liu, Ge Deng, Zi-Yao Ou, Shu-Fang Li, Xiao-Ling Xu, Mei-Ju Zhang, Xiao-Qing Peng, Fei-Hu Chen

Cell proliferation 2022 Mar

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This study aimed to investigate the biological impacts and possible mechanisms of a novel lncRNA, LncSIK1, in AML progression and retinoic acid-regulated AML cell development. The expression pattern of LncSIK1 was evaluated by qPCR and fluorescence in situ hybridization. CCK-8 assay, immunofluorescence, Wright-Giemsa staining, flow cytometry and Western blotting were performed to assess cell proliferation and differentiation. Bioluminescence imaging and H&E staining were used to detect AML progression in vivo. RNA or chromatin immunoprecipitation assays were conducted to measure the interaction of E2F1 and LncSIK1 or the LC3 and DRAM promoters. Autophagy was measured by transmission electron microscopy and Western blotting. LncSIK1 was silenced in bone marrow mononuclear cells from AML patients compared with those from healthy donors. LncSIK1 strengthened the effect of retinoic acid in inducing cell differentiation and inhibiting cell proliferation in AML cells. Moreover, the silencing of LncSIK1 was critical to maintaining AML leukaemogenesis, as LncSIK1 enhancement retarded AML progression in vivo. Mechanistically, in NB4 cells, LncSIK1 recruited the E2F1 protein to the promoters of LC3 and DRAM and induced autophagy-dependent degradation of the oncoprotein PML-RARa. However, LncSIK1 blocked E2F1 expression and the E2F1-mediated transcription of LC3 and DRAM, thereby relieving aggressive autophagy in Molm13 cells. Taken together, these data indicated that LncSIK1 was an important regulator of AML development through regulating the E2F1/autophagy signalling pathway. © 2022 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.

Citation

Ke Wang, Jun-da Liu, Ge Deng, Zi-Yao Ou, Shu-Fang Li, Xiao-Ling Xu, Mei-Ju Zhang, Xiao-Qing Peng, Fei-Hu Chen. LncSIK1 enhanced the sensitivity of AML cells to retinoic acid by the E2F1/autophagy pathway. Cell proliferation. 2022 Mar;55(3):e13185