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Cited by 231Cancer-related molecular mechanisms researchAngiogenesis and VEGF in CancerLymphatic System and Diseases

LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis

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Wang, Yirong, Wu, Siqi, Zhu, Xun, Zhang, Liyuan, Deng, Jieqiong, Li, Fang, Guo, Binbin, Zhang, Shenghua +5 more·2020·Journal of Experimental Medicine
DOI 10.1084/jem.20190950PMC PMC7062514
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Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) with the most aggressive phenotype and poor overall survival. Using bioinformatics tools, we identified LINC00908 encoding a 60–aa polypeptide and differentially expressed in TNBC tissues. We named this endogenously expressed polypeptide ASRPS (a small regulatory peptide of STAT3). ASRPS expression was down-regulated in TNBCs and associated with poor overall survival. We showed that LINC00908 was directly regulated by ERα, which was responsible for the differential down-regulation of LINC00908 in TNBCs. ASRPS directly bound to STAT3 through the coiled coil domain (CCD) and down-regulated STAT3 phosphorylation, which led to reduced expression of VEGF. In human endothelial cells, a mouse xenograft breast cancer model, and a mouse spontaneous BC model, ASRPS expression reduced angiogenesis. In a mouse xenograft breast cancer model, down-regulation of ASRPS promoted tumor growth, and ASRPS acted as an antitumor peptide. We presented strong evidence that LINC00908-encoded polypeptide ASRPS represented a TNBC-specific target for treatment.

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  • CCD has a large hydrophilic surface predominantly involved in recruitment of STAT3 to its receptor, essential for activation via SH2 domain-mediated receptor binding, phosphorylation, and nuclear translocation.

    “CCD has a large hydrophilic surface predominantly involved in the recruitment of STAT3 to its receptor [50], which is essential not only for its activation via SH2 domain‐mediated receptor binding but also for its activation via phosphorylation [51] and nuclear translocation [52].”

    From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [51]

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Research works printed but not linked: 43

  1. Anderson D.M., Anderson K.M., Chang C.L., Makarewich C.A., Nelson B.R., McAnally J.R., Kasaragod P., Shelton J.M., Liou J., Bassel-Duby R., and Olson E.N. 2015 A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell. 160: 595– 606. 10.1016/j.cell.2015.01.009 25640239 PMC4356254 · DOI · Paper page
  2. Bahhnassy A., Mohanad M., Shaarawy S., Ismail M.F., El-Bastawisy A., Ashmawy A.M., and Zekri A.R. 2015 Transforming growth factor-β, insulin-like growth factor I/insulin-like growth factor I receptor and vascular endothelial growth factor-A: prognostic and predictive markers in triple-negative and non-triple-negative breast cancer. Mol. Med. Rep. 12: 851– 864. 10.3892/mmr.2015.3560 25824321 PMC4438878 · DOI
  3. Banerjee K., and Resat H. 2016 Constitutive activation of STAT3 in breast cancer cells: A review. Int. J. Cancer. 138: 2570– 2578. 10.1002/ijc.29923 26559373 PMC4801660 · DOI · Paper page
  4. Brewster A.M., Chavez-MacGregor M., and Brown P. 2014 Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry. Lancet Oncol. 15: e625– e634. 10.1016/S1470-2045(14)70364-X 25456381 PMC4413447 · DOI
  5. Bromberg J.F., Wrzeszczynska M.H., Devgan G., Zhao Y., Pestell R.G., Albanese C., and Darnell J.E. Jr 1999 Stat3 as an oncogene. Cell. 98: 295– 303. 10.1016/S0092-8674(00)81959-5 10458605 · DOI · Paper page
  6. Chang R., Song L., Xu Y., Wu Y., Dai C., Wang X., Sun X., Hou Y., Li W., Zhan X., and Zhan L. 2018 Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis. Nat. Commun. 9: 3486 10.1038/s41467-018-05852-8 30154439 PMC6113304 · DOI
  7. Elias A.D. 2010 Triple-negative breast cancer: a short review. Am. J. Clin. Oncol. 33: 637– 645. 10.1097/COC.0b013e3181b8afcf 20023571 · DOI
  8. Fang Y., and Fullwood M.J. 2016 Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer. Genomics Proteomics Bioinformatics. 14: 42– 54. 10.1016/j.gpb.2015.09.006 26883671 PMC4792843 · DOI
  9. Foulkes W.D., Smith I.E., and Reis-Filho J.S. 2010 Triple-negative breast cancer. N. Engl. J. Med. 363: 1938– 1948. 10.1056/NEJMra1001389 21067385 · DOI
  10. Gandin V., Sikström K., Alain T., Morita M., McLaughlan S., Larsson O., and Topisirovic I. 2014 Polysome fractionation and analysis of mammalian translatomes on a genome-wide scale. J. Vis. Exp. (87). 10.3791/51455 PMC4189431 24893926 · DOI
  11. Huang J.Z., Chen M., Chen D., Gao X.C., Zhu S., Huang H., Hu M., Zhu H., and Yan G.R. 2017 A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth. Mol. Cell. 68: 171– 184.e6. 10.1016/j.molcel.2017.09.015 28985503 · DOI
  12. Huang M., Song K., Liu X., Lu S., Shen Q., Wang R., Gao J., Hong Y., Li Q., Ni D., 2018 a AlloFinder: a strategy for allosteric modulator discovery and allosterome analyses. Nucleic Acids Res. 46(W1): W451– W458. 10.1093/nar/gky374 29757429 PMC6030990 · DOI
  13. Huang X.J., Xia Y., He G.F., Zheng L.L., Cai Y.P., Yin Y., and Wu Q. 2018 b MALAT1 promotes angiogenesis of breast cancer. Oncol. Rep. 40: 2683– 2689. 30226550
  14. Jonsson P., Coarfa C., Mesmar F., Raz T., Rajapakshe K., Thompson J.F., Gunaratne P.H., and Williams C. 2015 Single-Molecule Sequencing Reveals Estrogen-Regulated Clinically Relevant lncRNAs in Breast Cancer. Mol. Endocrinol. 29: 1634– 1645. 10.1210/me.2015-1153 26426411 PMC4627604 · DOI
  15. Koduru S.V., Tiwari A.K., Leberfinger A., Hazard S.W., Kawasawa Y.I., Mahajan M., and Ravnic D.J. 2017 A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer. J. Cancer. 8: 578– 596. 10.7150/jca.17633 28367238 PMC5370502 · DOI
  16. Kong X., Liu W., and Kong Y. 2018 Roles and expression profiles of long non-coding RNAs in triple-negative breast cancers. J. Cell. Mol. Med. 22: 390– 394. 10.1111/jcmm.13327 28941134 PMC5742739 · DOI
  17. Korff T., and Augustin H.G. 1998 Integration of endothelial cells in multicellular spheroids prevents apoptosis and induces differentiation. J. Cell Biol. 143: 1341– 1352. 10.1083/jcb.143.5.1341 9832561 PMC2133072 · DOI
  18. Li W., Li H., Zhang L., Hu M., Li F., Deng J., An M., Wu S., Ma R., Lu J., and Zhou Y. 2017 Long non-coding RNA LINC00672 contributes to p53 protein-mediated gene suppression and promotes endometrial cancer chemosensitivity. J. Biol. Chem. 292: 5801– 5813. 10.1074/jbc.M116.758508 28232485 PMC5392574 · DOI
  19. Li Y., Jiang B., Wu X., Huang Q., Chen W., Zhu H., Qu X., Xie L., Ma X., and Huang G. 2018 Long non-coding RNA MIAT is estrogen-responsive and promotes estrogen-induced proliferation in ER-positive breast cancer cells. Biochem. Biophys. Res. Commun. 503: 45– 50. 10.1016/j.bbrc.2018.05.146 29792859 · DOI
  20. Li F., Li H., Zhang L., Li W., Deng J., An M., Wu S., Lu X., Ma R., Wang Y., 2019 X chromosome-linked long noncoding RNA lnc-XLEC1 regulates c-Myc-dependent cell growth by collaborating with MBP-1 in endometrial cancer. Int. J. Cancer. 145: 927– 940. 10.1002/ijc.32166 30698832 · DOI
  21. Liu Y.R., Jiang Y.Z., Xu X.E., Yu K.D., Jin X., Hu X., Zuo W.J., Hao S., Wu J., Liu G.Y., 2016 Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative breast cancer. Breast Cancer Res. 18: 33 10.1186/s13058-016-0690-8 26975198 PMC4791797 · DOI
  22. Lv M., Xu P., Wu Y., Huang L., Li W., Lv S., Wu X., Zeng X., Shen R., Jia X., 2016 LncRNAs as new biomarkers to differentiate triple negative breast cancer from non-triple negative breast cancer. Oncotarget. 7: 13047– 13059. 10.18632/oncotarget.7509 26910840 PMC4914340 · DOI
  23. Ma J., Zhang T., Novotny-Diermayr V., Tan A.L., and Cao X. 2003 A novel sequence in the coiled-coil domain of Stat3 essential for its nuclear translocation. J. Biol. Chem. 278: 29252– 29260. 10.1074/jbc.M304196200 12746441 · DOI · Paper page
  24. Matsumoto A., Pasut A., Matsumoto M., Yamashita R., Fung J., Monteleone E., Saghatelian A., Nakayama K.I., Clohessy J.G., and Pandolfi P.P. 2017 mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature. 541: 228– 232. 10.1038/nature21034 28024296 · DOI
  25. Mattagajasingh S.N., Yang X.P., Irani K., Mattagajasingh I., and Becker L.C. 2012 Activation of Stat3 in endothelial cells following hypoxia-reoxygenation is mediated by Rac1 and protein Kinase C. Biochim. Biophys. Acta. 1823: 997– 1006. 10.1016/j.bbamcr.2012.02.008 22791907 PMC3392026 · DOI
  26. Niu G., Wright K.L., Huang M., Song L., Haura E., Turkson J., Zhang S., Wang T., Sinibaldi D., Coppola D., 2002 Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene. 21: 2000– 2008. 10.1038/sj.onc.1205260 11960372 · DOI · Paper page
  27. Peng Z., Wei J., Lu X., Zheng H., Zhong X., Gao W., Chen Y., and Jing J. 2016 Treatment and survival patterns of Chinese patients diagnosed with breast cancer between 2005 and 2009 in Southwest China: An observational, population-based cohort study. Medicine (Baltimore). 95: e3865 10.1097/MD.0000000000003865 27336872 PMC4998310 · DOI
  28. Polycarpou-Schwarz M., Groß M., Mestdagh P., Schott J., Grund S.E., Hildenbrand C., Rom J., Aulmann S., Sinn H.P., Vandesompele J., and Diederichs S. 2018 The cancer-associated microprotein CASIMO1 controls cell proliferation and interacts with squalene epoxidase modulating lipid droplet formation. Oncogene. 37: 4750– 4768. 10.1038/s41388-018-0281-5 29765154 · DOI
  29. Ribatti D., Nico B., Ruggieri S., Tamma R., Simone G., and Mangia A. 2016 Angiogenesis and Antiangiogenesis in Triple-Negative Breast cancer. Transl. Oncol. 9: 453– 457. 10.1016/j.tranon.2016.07.002 27751350 PMC5067931 · DOI
  30. Rodríguez Bautista R., Ortega Gómez A., Hidalgo Miranda A., Zentella Dehesa A., Villarreal-Garza C., Ávila-Moreno F., and Arrieta O. 2018 Long non-coding RNAs: implications in targeted diagnoses, prognosis, and improved therapeutic strategies in human non- and triple-negative breast cancer. Clin. Epigenetics. 10: 88 10.1186/s13148-018-0514-z 29983835 PMC6020372 · DOI
  31. Son D., Kim Y., Lim S., Kang H.G., Kim D.H., Park J.W., Cheong W., Kong H.K., Han W., Park W.Y., 2019 miR-374a-5p promotes tumor progression by targeting ARRB1 in triple negative breast cancer. Cancer Lett. 454: 224– 233. 10.1016/j.canlet.2019.04.006 31004703 · DOI
  32. Wang Z., Katsaros D., Biglia N., Shen Y., Loo L., Yu X., Lin H., Fu Y., Chu W.M., Fei P., 2019 ERα upregulates the expression of long non-coding RNA LINC00472 which suppresses the phosphorylation of NF-κB in breast cancer. Breast Cancer Res. Treat. 175: 353– 368. 10.1007/s10549-018-05108-5 30830488 PMC6534447 · DOI
  33. Wei D., Le X., Zheng L., Wang L., Frey J.A., Gao A.C., Peng Z., Huang S., Xiong H.Q., Abbruzzese J.L., and Xie K. 2003 Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene. 22: 319– 329. 10.1038/sj.onc.1206122 12545153 · DOI
  34. Wu H., Zheng J., Deng J., Zhang L., Li N., Li W., Li F., Lu J., and Zhou Y. 2015 LincRNA-uc002yug.2 involves in alternative splicing of RUNX1 and serves as a predictor for esophageal cancer and prognosis. Oncogene. 34: 4723– 4734. 10.1038/onc.2014.400 25486427 · DOI
  35. Xia X., Li X., Li F., Wu X., Zhang M., Zhou H., Huang N., Yang X., Xiao F., Liu D., 2019 A novel tumor suppressor protein encoded by circular AKT3 RNA inhibits glioblastoma tumorigenicity by competing with active phosphoinositide-dependent Kinase-1. Mol. Cancer. 18: 131 10.1186/s12943-019-1056-5 31470874 PMC6716823 · DOI
  36. Yan J., Wang Q., Zou K., Wang L., Schwartz E.B., Fuchs J.R., Zheng Z., and Wu J. 2015 Inhibition of the JAK2/STAT3 signaling pathway exerts a therapeutic effect on osteosarcoma. Mol. Med. Rep. 12: 498– 502. 10.3892/mmr.2015.3439 25760445 · DOI
  37. Yang R., Xing L., Wang M., Chi H., Zhang L., and Chen J. 2018 Comprehensive Analysis of Differentially Expressed Profiles of lncRNAs/mRNAs and miRNAs with Associated ceRNA Networks in Triple-Negative Breast Cancer. Cell. Physiol. Biochem. 50: 473– 488. 10.1159/000494162 30308479 · DOI
  38. Yu X., Abdullahi A.Y., Wu S., Pan W., Shi X., Hu W., Tan L., Li K., Wang Z., and Li G. 2017 Prokaryotic Expression of α-13 Giardin Gene and Its Intracellular Localization in Giardia lamblia. BioMed Res. Int. 2017: 1603264 10.1155/2017/1603264 28286754 PMC5329650 · DOI
  39. Zhang T., Kee W.H., Seow K.T., Fung W., and Cao X. 2000 The coiled-coil domain of Stat3 is essential for its SH2 domain-mediated receptor binding and subsequent activation induced by epidermal growth factor and interleukin-6. Mol. Cell. Biol. 20: 7132– 7139. 10.1128/MCB.20.19.7132-7139.2000 10982829 PMC86266 · DOI · Paper page
  40. Zhang C.Y., Yu M.S., Li X., Zhang Z., Han C.R., and Yan B. 2017 a Overexpression of long non-coding RNA MEG3 suppresses breast cancer cell proliferation, invasion, and angiogenesis through AKT pathway. Tumour Biol. 39: 1010428317701311. 28635399
  41. Zhang Y., Wang D.L., Yan H.Y., Liao J.Y., He J.H., Hu K.S., Deng W.X., Wang Y.J., Xing H.T., Koeffler H.P., and Yin D. 2017 b Genome-wide study of ER-regulated lncRNAs shows AP000439.3 may function as a key regulator of cell cycle in breast cancer. Oncol. Rep. 38: 3227– 3237. 10.3892/or.2017.5975 29048636 · DOI
  42. Zhang M., Zhao K., Xu X., Yang Y., Yan S., Wei P., Liu H., Xu J., Xiao F., Zhou H., 2018 A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma. Nat. Commun. 9: 4475 10.1038/s41467-018-06862-2 30367041 PMC6203777 · DOI
  43. Zhang H., Zhang N., Liu Y., Su P., Liang Y., Li Y., Wang X., Chen T., Song X., Sang Y., 2019 Epigenetic regulation of NAMPT by NAMPT-AS drives metastatic progression in triple-negative breast cancer. Cancer Res. 79: 3347– 3359. 10.1158/0008-5472.CAN-18-3418 30940661 · DOI

Cited by

Sorted by citations

Authors
Wang, Y., Wu, S., Zhu, X., Zhang, L., Deng, J., Li, F., Guo, B., Zhang, S., Wu, R., Zhang, Z., Wang, K., Lu, J., & Zhou, Y.
Affiliations
  • Soochow University (CN)
  • Second Affiliated Hospital of Soochow University (CN)
  • The State Key Lab of Respiratory Disease, The First Affiliated Hospital, The School of Public Health, Guangzhou Medical University, Guangzhou, China 4
Corresponding author
Zhou, Yifeng
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2019-12-05
Volume
217
Issue
3
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20190950
PMC
PMC7062514
OpenAlex
W2991798444
Cited by
231
References
2
Citations by year
2026: 23 · 2025: 30 · 2024: 46 · 2023: 52 · 2022: 32 · 2021: 28 · 2020: 20
FWCI
6.33
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Scientific Foundation of China (81772544, 81972649)
  • Science Foundation for Distinguished Young Scholars in Jiangsu (BK20160008)
  • Priority Academic Program Development of Jiangsu Higher Education Institutions
  • National Key R&D Program of China (2016YFC1302100)
  • Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2017ZT07S096)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
Keywords
triple-negative breast cancer, STAT3, angiogenesis, estrogen receptor alpha, vascular endothelial growth factor, STAT3 phosphorylation, coiled-coil domain, anticancer peptides, tumor growth, prognostic factors
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Female, Humans, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Neovascularization, Pathologic, Peptides, Down-Regulation, Gene Expression Regulation, Neoplastic, Xenograft Model Antitumor Assays, Endothelial Cells, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor, HEK293 Cells, MCF-7 Cells, RNA, Long Noncoding, Triple Negative Breast Neoplasms

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