AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025510526
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ORIGINAL RESEARCH ARTICLE

Screening of potential autophagy-related long non-coding RNAs and their regulatory pathways in radioactive iodine-refractory differentiated thyroid cancer

Yingying Luo1,2 ,  Zengbei Yuan3 ,  Qiteng Lu1 ,  Junhong Li1 ,  Xiaoan Pang1 ,  Zhixiao Wei1* ,  Sijin Li4*
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1 Department of Nuclear Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
2 Radiology Department, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
3 School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, Fujian, China
4 Department of Nuclear Medicine, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
EJMO, 025510526 https://doi.org/10.36922/EJMO025510526
Received: 17 December 2025 | Revised: 22 February 2026 | Accepted: 30 March 2026 | Published online: 14 May 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Radioiodine-refractory differentiated thyroid cancer is associated with autophagy and long non-coding RNAs (lncRNAs). However, the underlying regulatory mechanisms remain unclear.

Objective: To investigate autophagy-related protein 14 (ATG14) expression in radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) and explore regulatory mechanisms of potential lncRNAs involved in autophagy-mediated RAIR-DTC.

Methods: A retrospective analysis included 72 patients with DTC who received ≥ 2 courses of radioactive iodine (131I) therapy (2013–2019). Patients were divided into RAIR-DTC and non-radioiodine-refractory (NRAIR-DTC) groups based on treatment response. Immunohistochemistry was used to assess ATG14 expression and its diagnostic value. RNA expression profiles were obtained via high-throughput sequencing to identify differentially expressed RNAs. A competing endogenous RNA (ceRNA) network was constructed using miRNA target prediction databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Key lncRNAs and mRNAs were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results: ATG14 expression was significantly higher in RAIR-DTC tissues than in NRAIR-DTC tissues before 131I therapy (t = 12.915, p < 0.05). Exploratory receiver operating characteristic curve analysis revealed an area under the curve of 0.995, with a threshold of 0.047, sensitivity of 94.6%, specificity of 100%, and 95% confidence interval: 0.987–1.000 (p < 0.01). Sequencing identified 21 differentially expressed genes (14 lncRNAs and 7 mRNAs). The predicted ceRNA network identified five potential lncRNAs, among which four lncRNAs (TMPO-AS1, LOC101060400, FAM239B, SLC5A4-AS1) may co-regulate the mRNA SLC1A7 via hsa-miR-1587. RT-qPCR revealed up-regulation of TMPO-AS1 and FLT3, and down-regulation of LOC101060400, FAM239B, SLC5A4-AS1, SLC1A7, IL5RA, and ETV7 in RAIR-DTC group.

Conclusion: ATG14 is highly expressed in RAIR-DTC and shows potential discriminatory ability, requiring further validation. A ceRNA network involving lncRNAs was predicted. TMPO-AS1 may regulate SLC1A7 via hsa-miR-1587, though this requires further validation. ATG14 and TMPO-AS1 may serve as potential therapeutic targets for RAIR-DTC.

Keywords
Iodine-refractory differentiated thyroid cancer
Autophagy-related protein 14
High-throughput sequencing
Long non-coding RNAs
Biomarkers
Funding
This study was supported by the Open Research Fund Program of Collaborative Innovation Center for Molecular Imaging of Precision Medicine (No. 2020- MS04); Guangxi Natural Science Foundation Project (No.2023GXNSFAA026069); The Guangxi Science Foundation Project (Gui Keji 0779027).
Conflict of interest
The authors declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492
  2. Qin Y, Sun W, Wang Z, et al. ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes. Mol Ther Nucleic Acids. 2020;22:584-600. doi: 10.1016/j.omtn.2020.09.022
  3. Qin Y, Sun W, Wang Z, et al. RBM47/SNHG5/FOXO3 axis activates autophagy and inhibits cell proliferation in papillary thyroid carcinoma. Cell Death Dis. 2022;13(3):270. doi: 10.1038/s41419-022-04728-6
  4. Wen D, Liu WL, Lu ZW, Cao YM, Ji QH, Wei WJ. SNHG9, a Papillary Thyroid Cancer Cell Exosome-Enriched lncRNA, Inhibits Cell Autophagy and Promotes Cell Apoptosis of Normal Thyroid Epithelial Cell Nthy-ori-3 Through YBOX3/P21 Pathway. Front Oncol. 2021;11:647034. doi: 10.3389/fonc.2021.647034
  5. Kocaturk NM, Akkoc Y, Kig C, Bayraktar O, Gozuacik D, Kutlu O. Autophagy as a molecular target for cancer treatment. Eur J Pharm Sci. 2019;134:116-137. doi: 10.1016/j.ejps.2019.04.011
  6. Fan W, Nassiri A, Zhong Q. Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L). Proc Natl Acad Sci USA. 2011;108(19):7769-7774. doi: 10.1073/pnas.1016472108
  7. Diao J, Liu R, Rong Y, et al. ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature. 2015;520(7548):563-566. doi: 10.1038/nature14147
  8. Zhu XJ, Jin X, Dai L, Liu X, Liu Z. ATG4 promotes cell proliferation, migration and invasion in HCC and predicts a poor prognosis. Eur Rev Med Pharmacol Sci. 2020;24(24):12686-12693. doi: 10.26355/eurrev_202012_24166
  9. Chu YH, Hardin H, Schneider DF, Chen H, Lloyd RV. MicroRNA-21 and long non-coding RNA MALAT1 are overexpressed markers in medullary thyroid carcinoma. Exp Mol Pathol. 2017;103(2):229-236. doi: 10.1016/j.yexmp.2017.10.002
  10. Yuan J, Song Y, Pan W, et al. LncRNA SLC26A4-AS1 suppresses the MRN complex-mediated DNA repair signaling and thyroid cancer metastasis by destabilizing DDX5. Oncogene. 2020;39(43):6664-6676. doi: 10.1038/s41388-020-01460-3
  11. Liu H, Deng H, Zhao Y, Li C, Liang Y. LncRNA XIST/miR- 34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling. J Exp Clin Cancer Res. 2018;37(1):279. doi: 10.1186/s13046-018-0950-9
  12. Yu X, Lin Q, Liu F, Yang F, Mao J, Chen X. LncRNA TMPO-AS1 facilitates the proliferation and metastasis of NSCLC cells by up-regulating ERBB2 via sponging miR-204-3p. Int J Immunopathol Pharmacol. 2020;34:2058738420958947. doi: 10.1177/2058738420958947
  13. Wang Z, Huang D, Huang J, Nie K, Li X, Yang X. lncRNA TMPO-AS1 Exerts Oncogenic Roles in HCC Through Regulating miR-320a/SERBP1 Axis. Onco Targets Ther. 2020;13:6539-6551. doi: 10.2147/OTT.S250355
  14. Zheng Q, Jia J, Zhou Z, Chu Q, Lian W, Chen Z. The Emerging Role of Thymopoietin-Antisense RNA 1 as Long Noncoding RNA in the Pathogenesis of Human Cancers. DNA Cell Biol. 2021;40(7):848-857. doi: 10.1089/dna.2021.0024
  15. Li Z, Feng Y, Zhang Z, Cao X, Lu X. TMPO-AS1 promotes cell proliferation of thyroid cancer via sponging miR-498 to modulate TMPO. Cancer Cell Int. 2020;20(1):294. doi: 10.1186/s12935-020-01334-4
  16. Ren W, Zhang J, Li W, et al. A Tumor-Specific Prognostic Long Non-Coding RNA Signature in Gastric Cancer. Med Sci Monit. 2016;22:3647-3657. doi: 10.12659/msm.901190
  17. Zhi F, Wang Q, Xue L, et al. The Use of Three Long Non- Coding RNAs as Potential Prognostic Indicators of Astrocytoma. PLoS One. 2015;10(8):e0135242. doi: 10.1371/journal.pone.0135242
  18. Liu R, Shen L, Lin C, et al. MiR-1587 Regulates DNA Damage Repair and the Radiosensitivity of CRC Cells via Targeting LIG4. Dose Response. 2020;18(2):1559325820936906. doi: 10.1177/1559325820936906
  19. Hu Z, Li W, Li M, et al. Screening of Graves’ disease susceptibility genes by whole exome sequencing in a three-generation family. BMC Med Genomics. 2021;14(1):46. doi: 10.1186/s12920-020-00865-z
  20. Borowczyk M, Szczepanek-Parulska E, Dębicki S, et al. High incidence of FLT3 mutations in follicular thyroid cancer: potential therapeutic target in patients with advanced disease stage. Ther Adv Med Oncol. 2020;12:1758835920907534. doi: 10.1177/1758835920907534
  21. Elena-Pérez S, Heredero-Jung DH, García-Sánchez A, et al. Molecular Analysis of IL-5 Receptor Subunit Alpha as a Possible Pharmacogenetic Biomarker in Asthma. Front Med (Lausanne). 2020;7:624576. doi: 10.3389/fmed.2020.624576
  22. Li H, Zhang Y, Zheng S. Comprehensive Analysis Identified ETV7 as a Potential Prognostic Biomarker in Bladder Cancer. Biomed Res Int. 2021;2021:8530186. doi: 10.1155/2021/8530186
  23. Sun T, Guan Q, Wang Y, et al. Identification of differentially expressed genes and signaling pathways in papillary thyroid cancer: a study based on integrated microarray and bioinformatics analysis. Gland Surg. 2021;10(2):629-644. doi: 10.21037/gs-20-673
  24. Zhao L, Jia Y, Liu Y, Han B, Wang J, Jiang X. Integrated Bioinformatics Analysis of DNA Methylation Biomarkers in Thyroid Cancer Based on TCGA Database. Biochem Genet. 2022;60(2):629-639. doi: 10.1007/s10528-021-10117-z
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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