Abnormal methylation mediated upregulation of LINC00857 boosts malignant progression of lung adenocarcinoma by modulating the miR-486-5p/NEK2 axis

Sep 21, 2026

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LINC00857 is frequently dysregulated across cancers, yet the DNA methylation status of its promoter region and the mechanisms driving lung adenocarcinoma (LUAD) progression are not well defined. Using bioinformatics, the study analyzed LINC00857 expression and methylation in LUAD and tested its role as a competitive endogenous RNA. Results show promoter hypomethylation drives LINC00857 overexpression, while its knockdown reduces proliferation, migration, invasion, lymph node metastasis, and enhances radiosensitivity. Downstream miR-486-5p and NEK2 were identified, supporting a methylation-mediated LINC00857–miR-486-5p/NEK2 regulatory axis.

LanguageEnglish

CategoryResearch & Report

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Pages14

Reading Time35 min

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INTRODUCTION

Background: LUAD burden and relapse

Epigenetics and DNA methylation in cancer

ceRNA regulation by lncRNAs

Prior evidence linking LINC00857 to cancers

DOI: 10.1111/crj.13765 ORIGINAL ARTICL E Abnormal methylation mediated upregulation of LINC00857 boosts malignant progression of lung adenocarcinoma by modulating the miR-486-5p/NEK2 axis Haoyu Fu 1 | Mingming Zhang 2 | Xiaohui Liu 2 | Yiming Yang 3 | Ying Xing 1 1Department of Radiation Oncology, Tangshan People’s Hospital, Tangshan, China 2Department of Thoracic Surgery, Tangshan People’s Hospital, Tangshan, China 3Department of Breast Surgery, Tangshan People’s Hospital, Tangshan, China Correspondence Haoyu Fu, Department of Radiation Oncology, Tangshan People’s Hospital, No.65 Shengli Road, Lunan District, Tangshan, Hebei 063001, China. Email: [fhy063001@163.com](fhy063001@163.com) Funding information Key Project Program of Medical Science Research in Hebei Province, Grant/Award Number: 20171286 1 | INTRODUCTION Abstract LINC00857 is frequently dysregulated in varying cancers, which in turn exerts carcinogenic effects; however, its DNA methylation status in promoter region and molecular mechanisms underlying the progression of lung adenocarcinoma (LUAD) remain rarely understood. Through bioinformatics analysis, we examined the expression state and methylation site of LINC00857 in LUAD and further investigated the properties of LINC00857 as a competitive endogenous RNA in the cancer progression. The current study revealed that the overexpression of LINC00857 in LUAD tissue and cells was mainly caused by the hypomethylation of the promoter region. LINC00857 knockdown prominently reduced cell proliferation, impeded cell migration and invasion, and restrained lymph node metastasis, with enhancing radiosensitivity. The effects of LINC00857 on tumor growth were also investigated in nude mice models. Subsequently, the downstream factors, miR-486-5p and NEK2, were screened, and the putative regulatory axis was examined. Overall, the regulatory effect of methylation-mediated LINC00857 overexpression on miR-486-5p/NEK2 axis may be a new mechanism for LUAD progression. KEYWORDS LINC00857, LUAD, metastasis, methylation, radiosensitivity cascade in those patients.4 Hence, elucidating mechanism underlying the LUAD occurrence and metastasis is criti- Each year, at least one million deaths are caused by lung cancer, which is mostly responsible for deathrate associated with cancer globally. Lung adenocarcinoma (LUAD) is a prevalent histology.1 LUAD is found almost exclusively in peripheral lung tissue and arises from smaller airways.2 Surgery is suggested for patients with early LUAD, but most patients are suffering from an early relapse, in the first 2 years, after complete resection,3 which could be attributed to metastatic cal to provide better treatment strategies for LUAD. Epigenetics is a major promising area within current biomedical fields.5 As a critical mechanism of epigenesis, DNA methylation is key in regulating gene expression, chromatin modification, genome imprinting, and stabilization.6 Abnormal DNA methylation is increasingly being associated with the pathogenesis of many human cancers.6 For example, in lung cancer, ADAMTS18 was hindered by promoter CpG methylation and enhanced This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd. Clin Respir J. 2024;18:e13765 . [https://doi.org/10.1111/crj.13765](https://doi.org/10.1111/crj.13765) [wileyonlinelibrary.com/journal/crj](wileyonlinelibrary.com/journal/crj) 1 of 14 cisplatin sensitivity through EGFR/AKT signaling.7 Hypomethylation-induced upregulation of cancer/testis antigen KK-LC-1 promoted the LUAD development via activation of Notch1/Hes1 signaling.8 DNA methylation pattern of cancer cells impacts levels of protein-coding genes and tumor-related lncRNAs. Zhi et al. reported a computatio

FAQs

What mechanism links LINC00857 overexpression to LUAD progression?

LINC00857 overexpression in LUAD is mainly driven by hypomethylation of its promoter region, which then activates downstream effects on cancer phenotypes.

What experimental effects does LINC00857 knockdown produce in LUAD cells?

LINC00857 knockdown reduces cell proliferation, impedes migration and invasion, restrains lymph node metastasis, and enhances radiosensitivity.

Which downstream axis is implicated by the study?

The study screens and examines downstream factors miR-486-5p and NEK2, proposing a methylation-mediated regulatory axis: LINC00857–miR-486-5p/NEK2.

Sep 21, 2026

Uploaded by Aurora