Long non-coding RNA AC122108.1 promotes lung adenocarcinoma brain metastasis and progression through the Wnt/β-catenin pathway by directly binding to aldolase A

Shaobin Feng; Huiling Liu; Peng Du; Xushuai Dong; Qi Pang; Hua Guo

doi:10.21037/atm-21-5707

Long non-coding RNA AC122108.1 promotes lung adenocarcinoma brain metastasis and progression through the Wnt/β-catenin pathway by directly binding to aldolase A

Ann Transl Med. 2021 Dec;9(23):1729. doi: 10.21037/atm-21-5707.

Authors

Shaobin Feng¹, Huiling Liu², Peng Du³, Xushuai Dong¹, Qi Pang¹, Hua Guo¹

Affiliations

¹ Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
³ Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Abstract

Background: Brain metastasis (BM) is a major pathological subtype of lung adenocarcinoma (LAD), but the pathogenic mechanisms of BM remain unclear. The potential prognostic biomarkers and therapeutic targets for BM of LAD urgently need to be identified. AC122108.1 is a recently discovered new long non-coding ribonucleic acid (RNA).

Methods: AC122108 was found to be overexpressed in a LAD BM cell model, and upregulated in 64.52% of LAD BM tissues. AC122108 is an independent factor of BM during LAD development; however, the molecular mechanisms and clinical significance of AC122108.1 in LAD have not yet been established. Additionally, in vitro and in vivo experiments showed that the direct binding of AC122108.1 with aldolase A (ALDOA) enhanced the proliferation, apoptosis, invasiveness, migration, and metastasis of LAD cells.

Results: This RNA-protein complex decreased the stability of the β-catenin destruction complex, leading to the accumulation of β-catenin in the cytoplasm and ultimately its translocation into the nucleus to activate Wnt(wingless/integrated)/β-catenin signaling.

Conclusions: Overall, AC122108.1 promotes LAD BM and its progression through the Wnt/β-catenin pathway by directly binding to ALDOA. This study provides insights into the regulatory mechanism of the LAD BM. AC122108.1 may serve as a potential therapeutic target and prognostic biomarker of LAD.

Keywords: AC122108.1; ALDOA; Lung adenocarcinoma (LAD); brain metastasis; β-catenin.