Exosomal lncRNA DOCK9-AS2 derived from cancer stem cell-like cells activated Wnt/β-catenin pathway to aggravate stemness, proliferation, migration, and invasion in papillary thyroid carcinoma
Open accessAbstract
Exosomal long non-coding RNAs (lncRNAs) are crucial factors that mediate the extracellular communication in tumor microenvironment. DOCK9 antisense RNA2 (DOCK9-AS2) is an exosomal lncRNA which has not been investigated in papillary thyroid carcinoma (PTC). Based on the result of differentially expressed lncRNAs in PTC via bioinformatics databases, we discovered that DOCK9-AS2 was upregulated in PTC, and presented elevation in plasma exosomes of PTC patients. Functionally, DOCK9-AS2 knockdown reduced proliferation, migration, invasion, epithelial-to-mesenchymal (EMT) and stemness in PTC cells. PTC-CSCs transmitted exosomal DOCK9-AS2 to improve stemness of PTC cells. Mechanistically, DOCK9-AS2 interacted with SP1 to induce catenin beta 1 (CTNNB1) transcription and sponged microRNA-1972 (miR-1972) to upregulate CTNNB1, thereby activating Wnt/β-catenin pathway in PTC cells. In conclusion, PTC-CSCs-derived exosomal lncRNA DOCK9-AS2 activated Wnt/β-catenin pathway to aggravate PTC progression, indicating that DOCK9-AS2 was a potential target for therapies in PTC.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
DOCK9 knockdown leads to reduced proliferation and migratory characteristics in papillary thyroid carcinoma.
“DOCK9 was recently implicated as a target for the alleviation of papillary thyroid carcinoma due to knockdown leading to reduced proliferation and migratory characteristics (123).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [123]
The Results section, “DOCK9-AS2 silence abrogated proliferation, migration, invasion, EMT, and stemness of PTC cells” (page unavailable), reports reduced proliferation and migration after DOCK9-AS2 knockdown. The cited paper studies knockdown of the lncRNA DOCK9-AS2, not DOCK9 itself, so it does not support the target named in the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Wnt/β-catenin signaling and disease
Clevers, H., & Nusse, R. (2012) · Cell · doi:10.1016/j.cell.2012.05.012 · Cited by 5,554 · see citing works
Flagged first, then by citations
Research works printed but not linked: 49
- [1]Sipos JA Mazzaferri EL Thyroid cancer epidemiology and prognostic variables Clin. Oncol. 2010 22 395 404 20627675
- [2]Hay ID Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940–1999): temporal trends in initial therapy and long-termoutcome in 2444 consecutively treated patients World J. Surg. 2002 26 879 885 12016468
- [3]Lundgren CI Hall P Dickman PW Zedenius J Clinically significant prognostic factors for differentiated thyroid carcinoma Cancer 2006 106 524 531 16369995
- [4]Yoon J-H Kim J Gorospe M Long noncoding RNA turnover Biochimie 2015 117 15 21 25769416 PMC4565787
- [5]Lei, J. J. et al. Long noncoding RNA CDKN2B-AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription. Faseb J. fj201802252R 10.1096/fj.201802252R (2019). 30870006 · DOI
- [6]Li W Increased levels of the long intergenic non-protein coding RNA POU3F3 promote DNA methylation in esophageal squamous cell carcinoma cells Gastroenterology 2014 146 1714 1726.e1715 24631494
- [7]Karreth FA In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma Cell 2011 147 382 395 22000016 PMC3236086
- [8]Fernando TR The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia Mol. Cancer 2017 16 126 126 28724437 PMC5517805
- [9]He W MSC-regulated lncRNA MACC1-AS1 promotes stemness and chemoresistance through fatty acid oxidation in gastric cancer Oncogene 2019 38 4637 4654 30742067 PMC6756048
- [10]Li Z Wang Y Hu R Xu R Xu W LncRNA B4GALT1-AS1 recruits HuR to promote osteosarcoma cells stemness and migration via enhancing YAP transcriptional activity Cell Prolif. 2018 51 e12504 30182452 PMC6528912
- [11]Chen F lncRNA PLAC2 activated by H3K27 acetylation promotes cell proliferation and invasion via the activation of Wnt/β‑catenin pathway in oral squamous cell carcinoma Int. J. Oncol. 2019 54 1183 1194 30720068 PMC6411352
- [12]Gupta RA Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis Nature 2010 464 1071 1076 20393566 PMC3049919
- [13]Feng J A novel lncRNA n384546 promotes thyroid papillary cancer progression and metastasis by acting as a competing endogenous RNA of miR-145-5p to regulate AKT3 Cell Death Dis. 2019 10 433 31160577 PMC6547665
- [14]Wang, Y. et al. MYH9 binds to lncRNA gene PTCSC2 and regulates FOXE1 in the 9q22 thyroid cancer risk locus. Proc. Natl Acad. Sci. USA10.1073/pnas.1619917114 (2017). PMC5255605 28049826
- [15]Wang C-H Identification of key lncRNAs associated with atherosclerosis progression based on public datasets Front. Genet. 2019 10 123 123 30873207 PMC6403132
- [16]Clarke MF Cancer stem cells—perspectives on current status and future directions: AACR workshop on cancer stem cells Cancer Res. 2006 66 9339 16990346
- [17]Batlle E Clevers H Cancer stem cells revisited Nat. Med. 2017 23 1124 28985214
- [18]Poleszczuk J Enderling H Cancer stem cell plasticity as tumor growth promoter and catalyst of population collapse Stem Cells Int. 2016 2016 3923527 3923527 26858759 PMC4686719
- [19]Cabrera MC Hollingsworth RE Hurt EM Cancer stem cell plasticity and tumor hierarchy World J. Stem Cells 2015 7 27 36 25621103 PMC4300934
- [20]Sun Z Wang L Dong L Wang X Emerging role of exosome signalling in maintaining cancer stem cell dynamic equilibrium J. Cell. Mol. Med. 2018 22 3719 3728 PMC6050499 29799161
- [21]Gao Y LINC00311 promotes cancer stem-like properties by targeting miR-330-5p/TLR4 pathway in human papillary thyroid cancer Cancer Med. 2020 9 1515 1528 31894666 PMC7013059
- [22]Tkach M Théry C Communication by extracellular vesicles: where we are and where we need to go Cell 2016 164 1226 1232 26967288
- [23]Théry C Zitvogel L Amigorena S Exosomes: composition, biogenesis and function Nat. Rev. Immunol. 2002 2 569 579 12154376
- [24]Valenti R Tumor-released microvesicles as vehicles of immunosuppression Cancer Res. 2007 67 2912 17409393
- [25]Gernapudi R Targeting exosomes from preadipocytes inhibits preadipocyte to cancer stem cell signaling in early-stage breast cancer Breast Cancer Res. Treat. 2015 150 685 695 25783182 PMC4385483
- [26]Harris DA Exosomes released from breast cancer carcinomas stimulate cell movement PLoS ONE 2015 10 e0117495 e0117495 25798887 PMC4370373
- [27]Wu, F. et al. Exosomes increased angiogenesis in papillary thyroid cancer microenvironment. Endocr. Relat. Cancer, 10.1530/erc-19-0008 (2019). 30870812 · DOI
- [28]Zheng R Exosome-transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression Mol. Cancer 2018 17 143 143 30285771 PMC6169076
- [29]Hwang WL Lan HY Cheng WC Huang SC Yang MH Tumor stem-like cell-derived exosomal RNAs prime neutrophils for facilitating tumorigenesis of colon cancer J. Hematol. Oncol. 2019 12 10 30683126 PMC6347849
- [30]Chen, X. et al. Deacetylation of β-catenin by SIRT1 regulates self-renewal and oncogenesis of liver cancer stem cells. Cancer Lett. 10.1016/j.canlet.2019.07.021 (2019). 31394122 · DOI
- [31]Wei CY Downregulation of RNF128 activates Wnt/β-catenin signaling to induce cellular EMT and stemness via CD44 and CTTN ubiquitination in melanoma J. Hematol. Oncol. 2019 12 21 30832692 PMC6399928
- [32]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 37 279 279 30463570 PMC6249781
- [33]Long Y Wang X Youmans DT Cech TR How do lncRNAs regulate transcription? Sci. Adv. 2017 3 eaao2110 eaao2110 28959731 PMC5617379
- [34]Zheng, Z. Q. et al. Long non-coding RNA FAM225A promotes nasopharyngeal carcinoma tumorigenesis and metastasis by acting as ceRNA to sponge miR-590-3p/miR-1275 and upregulate ITGB3. Cancer Res. 10.1158/0008-5472.can-19-0799 (2019). 31331909 · DOI
- [35]Zhao CC Lnc SMAD5-AS1 as ceRNA inhibit proliferation of diffuse large B cell lymphoma via Wnt/β-catenin pathway by sponging miR-135b-5p to elevate expression of APC Cell Death Dis. 2019 10 252 30874550 PMC6420660
- [36]Hardin, H. et al. Thyroid cancer stem-like cell exosomes: regulation of EMT via transfer of lncRNAs. Lab. Invest. 10.1038/s41374-018-0065-0 (2018). PMC6138523 29967342 · DOI
- [37]Ahn S-H Henderson YC Williams MD Lai SY Clayman GL Detection of thyroid cancer stem cells in papillary thyroid carcinoma J. Clin. Endocrinol. Metab. 2014 99 536 544 24302752 PMC3913805
- [38]De Falco V CD44 proteolysis increases CREB phosphorylation and sustains proliferation of thyroid cancer cells Cancer Res. 2012 72 1449 1458 22271686
- [39]Li M Estrogen receptor β upregulated by lncRNA-H19 to promote cancer stem-like properties in papillary thyroid carcinoma Cell Death Dis. 2018 9 1120 1120 30389909 PMC6214949
- [40]Xu J Liao K Zhou W Exosomes regulate the transformation of cancer cells in cancer stem cell homeostasis Stem Cells Int. 2018 2018 4837370 4837370 30344611 PMC6174755
- [41]Dragomir M Chen B Calin GA Exosomal lncRNAs as new players in cell-to-cell communication Transl. Cancer Res. 2018 7 S243 S252 30148073 PMC6107076
- [42]Cameselle-Teijeiro, J. M. et al. Cribriform-morular variant of thyroid carcinoma: a neoplasm with distinctive phenotype associated with the activation of the WNT/β-catenin pathway. Mod. Pathol. 10.1038/s41379-018-0070-2 (2018). 29785019 · DOI
- [43]Cho SW Therapeutic potential of Dickkopf-1 in wild-type BRAF papillary thyroid cancer via regulation of β-Catenin/E-cadherin signaling J. Clin. Endocrinol. Metab. 2014 99 E1641 E1649 24848709
- [45]Jain S Ghanghas P Rana C Sanyal SN Role of GSK-3β in regulation of canonical Wnt/β-catenin signaling and PI3-K/Akt oncogenic pathway in colon cancer Cancer Invest. 2017 35 473 483 28718684
- [46]Chen X SP1-induced lncRNA-ZFAS1 contributes to colorectal cancer progression via the miR-150-5p/VEGFA axis Cell Death Dis. 2018 9 982 30250022 PMC6155123
- [47]Rhee, H. et al. Keratin 19 expression in hepatocellular carcinoma is regulated by fibroblast-derived HGF via a MET-ERK1/2-AP1 and SP1 axis. Cancer Res. 10.1158/0008-5472.can-17-0988 (2018). 29363547 · DOI
- [48]Liu B MiR-29b/Sp1/FUT4 axis modulates the malignancy of leukemia stem cells by regulating fucosylation via Wnt/β-catenin pathway in acute myeloid leukemia J. Exp. Clin. Cancer Res. 2019 38 200 31097000 PMC6524323
- [49]Gavert N c-Kit is suppressed in human colon cancer tissue and contributes to L1-mediated metastasis Cancer Res. 2013 73 5754 5763 24008320
- [50]Wang Y Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma Mol. Cancer 2018 17 89 89 29753317 PMC5948795
Cited by
Sorted by citations
Thompson, A. P., Bitsina, C., Gray, J. L., von Delft, F., & Brennan, P. E. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100521 · Cited by 21 · see citing works
“DOCK9 was recently implicated as a target for the alleviation of papillary thyroid carcinoma due to knockdown leading to reduced proliferation and migratory characteristics (123).”
Background
- Authors
- Dai, W., Jin, X., Han, L., Huang, H., Ji, Z., Xu, X., Tang, M., Jiang, B., & Chen, W.
- Affiliations
- Nantong University (CN)
- Corresponding author
- Jiang, Bin
- Venue
- Cell Death & Disease
- Published
- 2020-09-11
- Volume
- 11
- Issue
- 9
- Pages
- 743-743
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC7486896
- OpenAlex
- W3086820975
- Cited by
- 79
- References
- 1
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 10 · 2023: 11 · 2022: 17 · 2021: 11 · 2020: 2
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- The study was supported by the Science and Technology Project of NanTong
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- long non-coding RNA, exosomes, papillary thyroid carcinoma, cancer stem cells, Wnt/β-catenin signaling, CTNNB1, Sp1, epithelial-mesenchymal transition, cancer stemness, cell proliferation, cell migration and invasion, plasma exosomes, tumor microenvironment
- MeSH terms
- Thyroid Cancer, Papillary, Animals, Cell Movement, Humans, Male, Mice, Nude, Neoplasm Invasiveness, Transfection, Neoplastic Stem Cells, Guanine Nucleotide Exchange Factors, Cell Proliferation, beta Catenin, Mice, Exosomes, RNA, Long Noncoding
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review