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2000
Volume 25, Issue 10
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Long non-coding RNAs (lncRNAs) play vital roles in the development and progression of various tumors through multiple mechanisms. Among these, HOTTIP (HOXA transcript at the distal tip) stands out as an intriguing candidate with diverse functions in several malignancies, including breast cancer and gynecologic cancers such as ovarian, cervical, and endometrial cancers, which are significant global health concerns. HOTTIP interacts with key signaling pathways associated with these cancers, including Wnt/β-catenin, PI3K/AKT, and MEK/ERK pathways, enhancing their activation and downstream effects. Its influence extends to crucial aspects of cancer biology, such as cell proliferation, apoptosis, migration, invasion, angiogenesis, and epithelial-mesenchymal transition (EMT). Additionally, HOTTIP plays a pivotal role in the pathogenesis of breast and gynecologic tumors by sponging various microRNAs (miRNAs) and regulating the expression of mRNAs involved in critical molecular processes. This dysregulation is often associated with poor clinical outcomes, advanced disease stages, and distant metastases. Understanding the functional roles of HOTTIP in these cancers is essential for developing targeted therapeutic strategies. This review aims to explore the emerging roles of HOTTIP in breast and gynecologic cancers.

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2025-01-06
2025-12-19
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References

  1. EkinciN. KaramanS.T. BasatO. Women’s knowledge levels in protection from gynecological cancers and affecting factors.Eur Arch Med Res2023394262268
    [Google Scholar]
  2. PourF.K. KeivanM. GhaedrahmatiF. Endometrial cancer stem cells related signaling pathways.Curr. Cancer Ther. Rev.202319428429110.2174/1573394719666230306145642
    [Google Scholar]
  3. CrosbieE.J. KitsonS.J. McAlpineJ.N. MukhopadhyayA. PowellM.E. SinghN. Endometrial cancer.Lancet2022399103331412142810.1016/S0140‑6736(22)00323‑3 35397864
    [Google Scholar]
  4. Gaona-LuvianoP. Medina-GaonaL.A. Magaña-PérezK. Epidemiology of ovarian cancer.Chin Clin Oncol2020944710.21037/cco‑20‑34 32648448
    [Google Scholar]
  5. PimpleS. MishraG. Cancer cervix: Epidemiology and disease burden.Cytojournal2022192110.25259/CMAS_03_02_2021 35510109
    [Google Scholar]
  6. MerloS. Modern treatment of vulvar cancer.Radiol. Oncol.202054437137610.2478/raon‑2020‑0053 32960779
    [Google Scholar]
  7. AdamsT.S. RogersL.J. CuelloM.A. Cancer of the vagina: 2021 update.Int. J. Gynaecol. Obstet.2021155S1Suppl. 1192710.1002/ijgo.13867 34669198
    [Google Scholar]
  8. Abouali Gale DariM. AnbiyaieeA. MoghanibashiM. Mohammad JafariR. MorameziF. FarzanehM. Exploring the Evolving Significance of lncRNA TUG1-mediated Signaling Pathways in Breast Cancer.Curr. Signal Transduct. Ther.2024191e19012422582210.2174/0115743624264761231212055008
    [Google Scholar]
  9. KhanM.M. YalamartyS.S.K. RajmalaniB.A. FilipczakN. TorchilinV.P. Recent strategies to overcome breast cancer resistance.Crit. Rev. Oncol. Hematol.202419710435110.1016/j.critrevonc.2024.104351 38615873
    [Google Scholar]
  10. ŁukasiewiczS. CzeczelewskiM. FormaA. BajJ. SitarzR. StanisławekA. Breast cancer—epidemiology, risk factors, classification, prognostic markers, and current treatment strategies—an updated review.Cancers20211317428710.3390/cancers13174287 34503097
    [Google Scholar]
  11. SonJ. CarrC. YaoM. Endometrial cancer in young women: Prognostic factors and treatment outcomes in women aged ≤40 years.Int. J. Gynecol. Cancer202030563163910.1136/ijgc‑2019‑001105 32213530
    [Google Scholar]
  12. SpeiserD. BickU. Primary prevention and early detection of hereditary breast cancer.Breast Care202318644845410.1159/000533391 38125920
    [Google Scholar]
  13. PontiG. De AngelisC. PontiR. Hereditary breast and ovarian cancer: From genes to molecular targeted therapies.Crit. Rev. Clin. Lab. Sci.202360864065010.1080/10408363.2023.2234488 37455374
    [Google Scholar]
  14. SokolovaA. JohnstoneK.J. McCart ReedA.E. SimpsonP.T. LakhaniS.R. Hereditary breast cancer: Syndromes, tumour pathology and molecular testing.Histopathology2023821708210.1111/his.14808 36468211
    [Google Scholar]
  15. BowdenS.J. DoulgerakiT. BourasE. Risk factors for human papillomavirus infection, cervical intraepithelial neoplasia and cervical cancer: An umbrella review and follow-up Mendelian randomisation studies.BMC Med.202321127410.1186/s12916‑023‑02965‑w 37501128
    [Google Scholar]
  16. KeyvaniV. KheradmandN. NavaeiZ.N. MollazadehS. EsmaeiliS.A. Epidemiological trends and risk factors of gynecological cancers: An update.Med. Oncol.20234039310.1007/s12032‑023‑01957‑3 36757546
    [Google Scholar]
  17. Golia D’AugèT. GianniniA. BoganiG. Prevention, screening, treatment and follow-up of gynecological cancers: state of art and future perspectives.Clin. Exp. Obstet. Gynecol.202350816010.31083/j.ceog5008160
    [Google Scholar]
  18. GitasG. PadosG. LaganàA.S. GuentherV. AckermannJ. AlkatoutI. Role of laparoscopic hysterectomy in cervical and endometrial cancer: A narrative review.Minim. Invasive Ther. Allied Technol.202332111110.1080/13645706.2022.2154166 36512487
    [Google Scholar]
  19. Hernandez-ZepedaM.L. MunroE.G. CaugheyA.B. BrueglA.S. Ovarian preservation compared to oophorectomy in premenopausal women with early-stage, low-grade endometrial Cancer: A cost-effectiveness analysis.Gynecol. Oncol.202317381410.1016/j.ygyno.2023.03.021 37030073
    [Google Scholar]
  20. LuY. ChenJ. WeiR. Application of robotic surgery and traditional laparoscopic surgery in lymph node dissection for gynecological cancer: A meta analysis.Oncol. Lett.202325517510.3892/ol.2023.13761 37033101
    [Google Scholar]
  21. Hitova-TopkarovaD. PayakovaV. Kostova-LefterovaD. IvanovaM. Vasileva-SlavevaM. YordanovA. Electronic brachytherapy for gynecological cancers - A systematic review.Rep. Pract. Oncol. Radiother.20232817987
    [Google Scholar]
  22. WysockiP.J. ŁobaczM. PotockiP. Metronomic chemotherapy based on topotecan or topotecan and cyclophosphamide combination (CyTo) in advanced, pretreated ovarian cancer.Cancers2023154106710.3390/cancers15041067 36831410
    [Google Scholar]
  23. WalshC.S. HackerK.E. SecordA.A. DeLairD.F. McCourtC. UrbanR. Molecular testing for endometrial cancer: An SGO clinical practice statement.Gynecol. Oncol.2023168485510.1016/j.ygyno.2022.10.024 36399812
    [Google Scholar]
  24. DoghishA.S. AliM.A. ElyanS.S. miRNAs role in cervical cancer pathogenesis and targeted therapy: Signaling pathways interplay.Pathol. Res. Pract.202324415438610.1016/j.prp.2023.154386 36868096
    [Google Scholar]
  25. MikhanovskyiA. KharchenkoY.V. Justification of the choice of hormone therapy for ovarian cancer.Infusion & Chemotherapy20234653
    [Google Scholar]
  26. MobinikhalediM. FaridzadehA. FarkhondehT. PourhanifehM.H. SamarghandianS. The roles of autophagy-related mirnas in gynecologic tumors: A review of current knowledge for possible targeted therapy.Curr. Mol. Med.202424101269128110.2174/0115665240263059231002093454 39300715
    [Google Scholar]
  27. LampropoulouD.I. PapadimitriouM. PapadimitriouC. The role of EMT-related lncRNAs in ovarian cancer.Int. J. Mol. Sci.202324121007910.3390/ijms241210079 37373222
    [Google Scholar]
  28. RazaviZ.S. TajikniaV. MajidiS. Gynecologic cancers and non-coding RNAs: Epigenetic regulators with emerging roles.Crit. Rev. Oncol. Hematol.202115710319210.1016/j.critrevonc.2020.103192 33290823
    [Google Scholar]
  29. GAO Y. Expression and clinical significance of long non-coding RNA HOTTIP in tissues of patients with endometrial carcinoma.Zhongguo Zhongliu Shengwu Zhiliao Zazhi202013781382
    [Google Scholar]
  30. NajafiS. GhaedrahmatiF. Abouali Gale DariM. FarzanehM. Mohammad JafariR. The regulatory role of circular RNAs as miRNA sponges in cervical cancer.Curr. Signal Transduct. Ther.2023183e24112322377710.2174/0115743624273536231105142321
    [Google Scholar]
  31. ZouT. WangP.L. GaoY. LiangW.T. Long noncoding RNA HOTTIP is a significant indicator of ovarian cancer prognosis and enhances cell proliferation and invasion.Cancer Biomark.201925213313910.3233/CBM‑181727 30452402
    [Google Scholar]
  32. ZhuS-K. ZhangY. XuT. YangC. ZhongS. RanQ. Prognostic value of long non-coding RNA HOTTIP as a novel biomarker in various cancers: A meta-analysis.Tumour Biol.2017391010428317715530
    [Google Scholar]
  33. AbdiE. Latifi-NavidS. ZahriS. SNP-SNP interactions of oncogenic long non-coding RNAs HOTAIR and HOTTIP on gastric cancer susceptibility.Sci. Rep.20201011676310.1038/s41598‑020‑73682‑0 33028884
    [Google Scholar]
  34. LvZ. XuQ. SunL. Four novel polymorphisms in long non-coding RNA HOTTIP are associated with the risk and prognosis of colorectal cancer.Biosci. Rep.2019395BSR2018057310.1042/BSR20180573 30940774
    [Google Scholar]
  35. SunY. HuB. WangQ. Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR-216a.Cell Death Dis.2018928510.1038/s41419‑017‑0113‑5 29367594
    [Google Scholar]
  36. SinghA.P. LuoH. MaturM. A coordinated function of lncRNA HOTTIP and miRNA-196b underpinning leukemogenesis by targeting FAS signaling.Oncogene202241571873110.1038/s41388‑021‑02127‑3 34845377
    [Google Scholar]
  37. BrewerG. WilsonG.M. Introduction to RNA and Cancer.RNA-based Mechanisms in Cancer.World Scientific2024112
    [Google Scholar]
  38. LiuT. WangH. YuH. The long non-coding RNA HOTTIP is highly expressed in colorectal cancer and enhances cell proliferation and invasion.Mol. Ther. Nucleic Acids20201961261810.1016/j.omtn.2019.12.008 31945724
    [Google Scholar]
  39. HaoY. ZhuG. YuL. RenZ. ZhouW. ZhangP. FOXO3-activated HOTTIP sequesters MiR-615-3p away from COL2A1 to mitigate intervertebral disc degeneration.Am. J. Pathol.2023 37981220
    [Google Scholar]
  40. WangF. TangZ. ShaoH. Long noncoding RNA HOTTIP cooperates with CCCTC-binding factor to coordinate HOXA gene expression.Biochem. Biophys. Res. Commun.2018500485285910.1016/j.bbrc.2018.04.173 29698677
    [Google Scholar]
  41. LiuR. LiZ. SongE. LncRNA HOTTIP enhances human osteogenic BMSCs differentiation via interaction with WDR5 and activation of Wnt/β-catenin signalling pathway.Biochem. Biophys. Res. Commun.202052441037104310.1016/j.bbrc.2020.02.034 32067741
    [Google Scholar]
  42. ZengX. DongQ. LiuQ. TanW.J. LiuX.D. LncRNA HOTTIP facilitates osteogenic differentiation in bone marrow mesenchymal stem cells and induces angiogenesis via interacting with TAF15 to stabilize DLX2.Exp. Cell Res.2022417211322610.1016/j.yexcr.2022.113226 35644412
    [Google Scholar]
  43. ShangA. WangW. GuC. Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils.J. Exp. Clin. Cancer Res.201938141110.1186/s13046‑019‑1394‑6 31533774
    [Google Scholar]
  44. LiuJ. HuH.B. LiuY.M. LiF.X. ZhangL.P. LiaoZ.M. LncRNA HOTTIP promotes the proliferation and invasion of ovarian cancer cells by activating the MEK/ERK pathway.Mol. Med. Rep.20202253667367610.3892/mmr.2020.11452 33000231
    [Google Scholar]
  45. TanC. LiuW. ZhengZ.H. WanX.G. LncRNA HOTTIP inhibits cell pyroptosis by targeting miR‐148a‐3p/AKT2 axis in ovarian cancer.Cell Biol. Int.20214571487149710.1002/cbin.11588 33710684
    [Google Scholar]
  46. DongY.J. FengW. LiY. HOTTIP-miR-205-ZEB2 axis confers cisplatin resistance to ovarian cancer cells.Front. Cell Dev. Biol.2021970742410.3389/fcell.2021.707424 34322490
    [Google Scholar]
  47. ZhangS. MaQ. WuX. ChenP. LncRNA hottip promotes ovarian cancer cell invasion and metastasis by stabilizing HIF-1α in the anoxic cellular microenvironment.Acta Endocrinol.202218326327010.4183/aeb.2022.263 36699159
    [Google Scholar]
  48. KhatoonE. ParamaD. KumarA. Targeting PD-1/PD-L1 axis as new horizon for ovarian cancer therapy.Life Sci.202230612082710.1016/j.lfs.2022.120827 35907493
    [Google Scholar]
  49. XuH. LuM. LiuY. RenF. ZhuL. Identification of a pyroptosis-related long non-coding RNA Signature for prognosis and its related ceRNA regulatory network of ovarian cancer.J. Cancer202314163151316810.7150/jca.88485 37859811
    [Google Scholar]
  50. YangY. QianJ. XiangY. ChenY. QuJ. The prognostic value of long noncoding RNA HOTTIP on clinical outcomes in breast cancer.Oncotarget2017846833684410.18632/oncotarget.14304 28036281
    [Google Scholar]
  51. SunY. ZengC. GanS. LncRNA HOTTIP-mediated HOXA11 expression promotes cell growth, migration and inhibits cell apoptosis in breast cancer.Int. J. Mol. Sci.201819247210.3390/ijms19020472 29415429
    [Google Scholar]
  52. GaoW. WuX.L. LiD.Z. LiuH.D. HOTTIP participates in mammary cancer by promoting cell proliferation via PI3K/AKT pathway.Eur. Rev. Med. Pharmacol. Sci.2018221341814187 30024606
    [Google Scholar]
  53. HanS. JinX. LiuZ. The long noncoding RNA HOTTIP promotes breast cancer cell migration, invasiveness, and epithelial–mesenchymal transition via the Wnt–β-catenin signaling pathway.Biochem. Cell Biol.201997565566410.1139/bcb‑2018‑0313 30676763
    [Google Scholar]
  54. HanL. YanY. ZhaoL. LncRNA HOTTIP facilitates the stemness of breast cancer via regulation of miR‐148a‐3p/WNT1 pathway.J. Cell. Mol. Med.202024116242625210.1111/jcmm.15261 32307830
    [Google Scholar]
  55. AbdelaleemO.O. ShakerO.G. AbdelHafezM.N. The influence of rs1859168 polymorphism on serum expression of HOTTIP and its target miR-615-3p in Egyptian patients with breast cancer.Biomolecules202111573310.3390/biom11050733 34069089
    [Google Scholar]
  56. LiuF. Effect of lncRNA HOTTIP on proliferation, migration and invasion of cervical cancer cells.Military Medical Sciences2015443-447452
    [Google Scholar]
  57. ChuntaoW. AnxingG. HongyanW. XueyanZ. ShengY. HongxiangY. The association between cervical lesions of different grades and lncRNA HOTTIP and H19 single nucleotide polymorphisms.China Oncology202232324334
    [Google Scholar]
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