Research Paper|Volume 15, Issue 9|pp 3538—3548

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

Zhen Zhang^1,², Xiaoning Tan¹, Ruoxia Wu², Tianhao Deng¹, Huazhong Wang¹, Xiulin Jiang^3,⁴, Puhua Zeng¹, Junqi Tang⁵

¹Department of Oncology, Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha 410006, P.R. China
²School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, P.R. China
³Department of Medicine, UF Health Cancer Center, University of Florida, Gainesville, FL 32611, USA
⁴Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650201, P.R. China
⁵Department of Respiratory Medicine, Hospital of Traditional Chinese Medicine, Affiliated to Southwest Medical University, Luzhou 646000, P.R. China

* Equal contribution

Received: February 6, 2023Accepted: April 17, 2023Published: May 3, 2023

https://doi.org/10.18632/aging.204689

Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.