m6A-mediated upregulation of lncRNA-AC026356.1 promotes cancer stem cell maintenance in lung adenocarcinoma via activating Wnt signaling pathway

Abstract

LncRNA plays a pivotal role in the stemness and drug resistance of lung cancer. Here, we found that lncRNA-AC026356.1 was upregulated in stem spheres and chemo-resistant lung cancer cells. Our fish assay also shows that AC026356.1 was predominantly located in the cytoplasm of lung cancer cells and does not have protein-coding potential. Silencing AC026356.1 significantly inhibited proliferation and migration but increased apoptosis in A549-cisplatin (DDP) cells. Additionally, IGF2BP2 and the lncRNA-AC026356.1 positively regulated the proliferation and stemness of stem-like lung cancer cells. Further mechanistic investigation revealed that METTL14/IGF2BP2-mediated m6A modification and stabilization of the AC026356.1 RNA. Functional analysis corroborated that AC026356.1 acted as a downstream target of METTL14/IGF2BP2 and AC026356.1 silencing could block the oncogenicity of lung cancer stem-like cells. AC026356.1 expression was correlated with immune cell infiltration and T cell exhaustion. Compared with paired adjacent normal tissues, lung cancer specimens exhibited consistently upregulated METTL14/IGF2BP2/AC026356.1. M6A-modified METTL14/IGF2BP2/AC026356.1 loop may serve as a potential therapeutic target and prognostic predictor for lung cancer therapy and diagnosis in the clinic.

Insulin-like growth factor 2 mRNA-binding protein 2 is a therapeutic target in ovarian cancer

“…34 IGF2BP2 can enhance the stability of lncRNA-AC026356.1 in lung cancer A549cisplatin cells, whereas lncRNA-AC026356.1 positively correlates with immune cells such as Th1 and Tem cells and negatively correlates with T-cell exhaustion. 35 Recently, the remarkable advancements of immunotherapy have made revolutionary changes in the treatment of cancer because of the understanding of the characteristics of the immune microenvironment. Therefore, immune checkpoint inhibitors, including CTLA-4 and its ligand B7/CD8, and PD-1 and its ligand PD-L1, 36 may apply to cancer patients.…”

Crosstalk between lncRNAs and Wnt/β-catenin signaling pathways in lung cancers: From cancer progression to therapeutic response

“…Moreover, m6A-mediated up-regulation of lncRNA-AC026356.1 induced cell stemness by the mediation of upstream molecule METTL14 and IGF2BP2. It suggests that there might be a METTL14/IGF2BP2/AC026356.1 loop that regulates cancer stemness via activating Wnt signaling pathway in LUAD [ 53 ].…”

“…Researchers have demonstrated that m6A-mediated AC026356.1 expression was substantially up-regulated in stem cells and chemoresistant LC cells. As a result, silencing AC026356.1 markedly suppressed proliferation and migration but increased apoptosis in A549/DDP cells [ 53 ]. By suppressing proliferation but increasing apoptosis, NEAT 1 knockdown sensitizes NSCLC cells to chemotherapy.…”

New insights into the interaction between m6A modification and lncRNA in cancer drug resistance

“…The upregulated AC026356.1 has been shown to play a crucial role in the maintenance of cancer cell stemness by activating the Wnt signalling pathway 112 in LUAD.…”

“… 111 Moreover, the stability of AC026356.1 was enhanced and its expression level was increased by the combined action of METTL14 and IGF2BP2. The upregulated AC026356.1 has been shown to play a crucial role in the maintenance of cancer cell stemness by activating the Wnt signalling pathway 112 in LUAD.…”