Abstract
Objectives
lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) acts as an oncogene involved in papillary thyroid carcinoma (PTC) occurrence and progression. ABHD11-AS1 exerts biologic functions by some miRNAs and proteins to regulate multiple targets. Identification of novel mechanism of ABHD11‐AS1 could be helpful in therapeutic targeting for PTC treatment.
Methods
Differentially expressed lncRNAs were selected from TCGA database. qRT‐PCR analysis was applied to examine the expression of ABHD11‐AS1 in PTC cell lines and tissues. The relationship of ABHD11-AS1 expression and clinicopathological features was analyzed by Kaplan–Meier analysis.
Two PTC cell lines (TPC-1 and KTC-1) were transfected with pcDNA 3.1, pcDNA3.1-ABHD11-AS1, si-NC and si-ABHD11-AS1, respectively, to verify the ABHD11-AS1 oncogene-regulating capacity to promote tumor progression. The cell metastasis and proliferation had been evaluated both in vitro and in vivo.
Results
High expression of ABHD11‐AS1 was found in PTC tissues (P < 0.01), which was significantly correlated with lymph node metastasis (P < 0.05). ABHD11-AS1 overexpression noticeably promoted cell proliferation, migration, and invasion capabilities, which were obviously decreased upon ABHD11-AS1 knockdown. ABHD11-AS1 positively regulated EGFR/EPS15L1 pathway, as EGFR, EPS15L1, STAT3, and p-STAT3 were activated.
Conclusion
ABHD11‐AS1 promotes tumor progression in PTC by regulating EPS15L1/EGFR pathway.
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Data availability statement
The data used to support the findings of this study are included within the article.
References
Xie SH, et al. Time trends and age-period-cohort analyses on incidence rates of thyroid cancer in Shanghai and Hong Kong. BMC Cancer. 2014;14:975.
Du L, et al. Incidence and mortality of thyroid cancer in China, 2008–2012. Chin J Cancer Res. 2019;31(1):144–51.
Agrawal N, et al. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676.
You X, et al. Molecular characterization of papillary thyroid carcinoma: a potential three-lncRNA prognostic signature. Cancer Manag Res. 2018;10:4297–310.
Shen CT, et al. Targeted next-generation sequencing in papillary thyroid carcinoma patients looking for germline variants predisposing to the disease. Endocrine. 2019;64(3):622–31.
Lundgren CI, et al. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer. 2006;106(3):524–31.
Lu H, et al. Markers of immune activation: novel biomarkers to predict the early-warning indicator of patients with papillary thyroid carcinoma. Diagn Pathol. 2020;15(1):16.
Yamashita H, et al. Extracapsular invasion of lymph node metastasis. A good indicator of disease recurrence and poor prognosis in patients with thyroid microcarcinoma. Cancer. 1999;86(5):842–9.
Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152(6):1298–307.
Dolcino M, et al. Long non-coding RNAs play a role in the pathogenesis of psoriatic arthritis by regulating microRNAs and genes involved in inflammation and metabolic syndrome. Front Immunol. 2018;9:1533.
Zhuang X, et al. Long noncoding RNA ABHD11-AS1 functions as a competing endogenous RNA to regulate papillary thyroid cancer progression by miR-199a-5p/SLC1A5 axis. Cell Death Dis. 2019;10(8):620.
He D, et al. Long noncoding RNA ABHD11-AS1 promote cells proliferation and invasion of colorectal cancer via regulating the miR-1254-WNT11 pathway. J Cell Physiol. 2019;234(7):12070–9.
Liu Y, et al. LncRNA ABHD11-AS1 promotes the development of endometrial carcinoma by targeting cyclin D1. J Cell Mol Med. 2018;22(8):3955–64.
Wu DD, et al. Role of the lncRNA ABHD11-AS(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC. Mol Cancer. 2017;16(1):138.
Liu Y, et al. Circulating lncRNA ABHD11-AS1 serves as a biomarker for early pancreatic cancer diagnosis. J Cancer. 2019;10(16):3746–56.
Chen M, et al. Increased lncRNA ABHD11-AS1 represses the malignant phenotypes of bladder cancer. Oncotarget. 2017;8(17):28176–86.
Lin X, et al. Increased expression of long noncoding RNA ABHD11-AS1 in gastric cancer and its clinical significance. Med Oncol. 2014;31(7):42.
Wen J, et al. STAT3-induced upregulation of lncRNA ABHD11-AS1 promotes tumour progression in papillary thyroid carcinoma by regulating miR-1301–3p/STAT3 axis and PI3K/AKT signalling pathway. Cell Prolif. 2019;52(2):e12569.
Tripathi V, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell. 2010;39(6):925–38.
Jin M, et al. Genetic Profiles of Aggressive Variants of Papillary Thyroid Carcinomas. Cancers (Basel). 2021;13(4):892.
Bertoni APS, et al. The gene expression of GPER1 is low in fresh samples of papillary thyroid carcinoma (PTC), and in silico analysis. Mol Cell Endocrinol. 2021;535:111397.
Huarte M, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142(3):409–19.
Yap KL, et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell. 2010;38(5):662–74.
Tseng YY, et al. PVT1 dependence in cancer with MYC copy-number increase. Nature. 2014;512(7512):82–6.
Chen C, et al. Long noncoding RNA CNALPTC1 promotes cell proliferation and migration of papillary thyroid cancer via sponging miR-30 family. Am J Cancer Res. 2018;8(1):192–206.
Gou Q, et al. Long noncoding RNA AB074169 inhibits cell proliferation via modulation of KHSRP-mediated CDKN1a expression in papillary thyroid carcinoma. Can Res. 2018;78(15):4163–74.
Sun W, et al. NEAT1_2 functions as a competing endogenous RNA to regulate ATAD2 expression by sponging microRNA-106b-5p in papillary thyroid cancer. Cell Death Dis. 2018;9(3):380.
Wu S, et al. Preparation of a novel EGFR specific immunotoxin and its efficacy of anti-colorectal cancer in vitro and in vivo. Clin Transl Oncol. 2021;23(8):1549–60.
Zheng Q, et al. A novel STAT3 inhibitor W2014-S regresses human non-small cell lung cancer xenografts and sensitizes EGFR-TKI acquired resistance. Theranostics. 2021;11(2):824–40.
Umair M, et al. First direct evidence of involvement of a homozygous loss-of-function variant in the EPS15L1 gene underlying split-hand/split-foot malformation. Clin Genet. 2018;93(3):699–702.
Guo M, et al. The landscape of long noncoding RNA-involved and tumor-specific fusions across various cancers. Nucleic Acids Res. 2020;48(22):12618–31.
Liang J, et al. The role of anlotinib-mediated EGFR blockade in a positive feedback loop of CXCL11-EGF-EGFR signalling in anaplastic thyroid cancer angiogenesis. Br J Cancer. 2021;125(3):390–401.
Acknowledgements
The work was supported by Department of Science and Technology of Zhejiang Province (LGF20H160029 and LGD20H160004).
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HL: Study design, formal analysis, writing—original draft, writing—review and editing; CZ: methodology, formal analysis, writing—original draft; YC: methodology, formal analysis, visualization; YR: methodology and visualization; LF: formal analysis; QC: conceptualization, study design, supervision, writing—review and editing; QW: conceptualization, formal analysis, writing—review and editing.
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All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional and/ or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.This study was approved by the Ethics Committee of Taizhou Central Hospital (2019-057).
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Lu, H., Zhu, C., Chen, Y. et al. LncRNA ABHD11-AS1 promotes tumor progression in papillary thyroid carcinoma by regulating EPS15L1/EGFR signaling pathway. Clin Transl Oncol 24, 1124–1133 (2022). https://doi.org/10.1007/s12094-021-02753-z
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DOI: https://doi.org/10.1007/s12094-021-02753-z