Top

Discover Oncology

Published in:

Open Access 01-12-2023 | Ovarian Cancer | Research

LncRNA HOTAIR down-expression inhibits the invasion and tumorigenicity of epithelial ovarian cancer cells by suppressing TGF-β1 and ZEB1

Authors: Yufu Zhou, Yunjie Zhang, Yidan Shao, Xiaoli Yue, Yifan Chu, Cuiping Yang, Dengyu Chen

Published in: Discover Oncology | Issue 1/2023

Abstract

Background

Epithelial ovarian cancer (EOC) is a pathological type with a higher mortality rate among gynecological cancers today. Long-chain noncoding RNAs (lncRNAs) can regulate the transcription and expression of cellular genes. However, the downstream molecules regulated by lncRNA HOTAIR have not been well studied. The effects of downregulated lncRNA HOTAIR on EOC invasiveness and tumorigenicity in nude mice, along with TGF- β1 and ZEB1 in epithelial ovarian cancer cells, need to be investigated in further research.

Results

RT-qPCR was used to detect lncRNA HOTAIR and TGF-β1 and ZEB1 mRNA expression in EOC SKOV3 cells. The expression of lncRNA HOTAIR in SKOV3 cells transfected with the recombinant shHOTAIR interference plasmid was significantly lower than that of the negative control. Compared with the negative control, the matrix gel invasion ability of shHOTAIR SKOV3 cells in vitro and their tumorigenicity in nude mice were significantly reduced. Moreover, compared with the control, the expression of ZEB1 protein in shHOTAIR-SKOV3 xenograft tumors was significantly reduced. Downregulation of lncRNA HOTAIR expression significantly reduced TGF-β1 and ZEB1 mRNA expression, but increased the expression of E-cadherin mRNA. In summary, downregulated lncRNA HOTAIR in EOC SKOV3 cells transfected with shHOTAIR can inhibit TGF-β1, reduce ZEB1, increase E-cadherin, and significantly reduce the invasiveness and tumorigenicity of ovarian epithelial cancer SKOV3 cells.

Conclusions

These results suggest that the lncRNA HOTAIR may be an effective target for the treatment of human EOC.

Available only for authorised users

Rickard BP, Conrad C, Sorrin AJ, et al. Malignant ascites in ovarian cancer: cellular, acellular, and biophysical determinants of molecular characteristics and therapy response. Cancers. 2021;13(17):4318. https://doi.org/10.3390/cancers13174318.CrossRefPubMedPubMedCentral

Cummings M, Nicolais O, Shahin M. Surgery in advanced ovary cancer: primary versus interval cytoreduction. Diagnostics. 2022;12(4):988. https://doi.org/10.3390/diagnostics12040988.CrossRefPubMedPubMedCentral

Tang PCT, Zhang YY, Li JSF, et al. LncRNA—dependent mechanisms of transforming growth factor-β: from tissue fibrosis to cancer progression. Noncoding RNA. 2022;8(3):36. https://doi.org/10.3390/ncrna8030036.CrossRefPubMedPubMedCentral

Ren Y, Jia HH, Yi-qi X, et al. Paracrine and epigenetic control of CAF-induced metastasis: the role of HOTAIR stimulated by TGF-ß1 secretion. Mol Cancer. 2018;17:5. https://doi.org/10.1186/s12943-018-0758-4.CrossRefPubMedPubMedCentral

Wang J, Chen D, He X, et al. Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorigenesis and metastasis by inhibiting epithelial-mesenchymal transition. Cancer Cell Int. 2015;15:24. https://doi.org/10.1186/s12935-015-0174-4.CrossRefPubMedPubMedCentral

Yang C, Li H, Zhang T, et al. miR-200c overexpression inhibits the invasion and tumorigenicity of epithelial ovarian cancer cells by suppressing lncRNA HOTAIR in mice. J Cell Biochem. 2020;121(2):1514–23. https://doi.org/10.1002/jcb.29387.CrossRefPubMed

Wang J, Liu X, Li P, et al. Long noncoding RNA HOTAIR regulates the stemness of breast cancer cells via activation of the NF-κB signaling pathway. J Biol Chem. 2022;298(12): 102630. https://doi.org/10.1016/j.jbc.2022.102630.CrossRefPubMedPubMedCentral

Jarroux J, Foretek D, Bertrand C, et al. HOTAIR lncRNA promotes epithelial–mesenchymal transition by redistributing LSD1 at regulatory chromatin regions. EMBO Rep. 2021;22(7): e50193. https://doi.org/10.15252/embr.202050193.CrossRefPubMedPubMedCentral

Feldker N, Ferrazzi F, Schuhwerk H, et al. Genome-wide cooperation of EMT transcription factor ZEB1 with YAP and AP-1 in breast cancer. EMBO J. 2020;39(17): e103209. https://doi.org/10.15252/embr.202050193.CrossRefPubMedPubMedCentral

10.

Chen DY, Zhang YX, Wang J, et al. MicroRNA-200c overexpression inhibits tumorigenicity and metastasis of CD117+CD44+ ovarian cancer stem cells by regulating epithelial-mesenchymal transition. J Ovarian Res. 2013;6:50. https://doi.org/10.1186/1757-2215-6-50.CrossRefPubMedPubMedCentral

11.

Raju GSR, Pavitra E, Bandaru SS, et al. HOTAIR: a potential metastatic drug-resistant and prognostic regulator of breast cancer. Mol Cancer. 2023. https://doi.org/10.1186/s12943-023-01765-3.CrossRefPubMedPubMedCentral

12.

Shi F, Chen X, Wang Y, et al. HOTAIR/miR-203/CAV1 crosstalk influences proliferation, migration, and invasion in the breast cancer cell. Int J Mol Sci. 2022;23(19):11755. https://doi.org/10.3390/ijms231911755.CrossRefPubMedPubMedCentral

13.

Nakayama F, Miyoshi M, Kimoto Ai, et al. Pancreatic cancer cell-derived exosomes induce epithelial-mesenchymal transition in human pancreatic cancer cells themselves partially via transforming growth factor β1. Med Mol Morphol. 2022;55(3):227–35. https://doi.org/10.1007/s00795-022-00321-0.CrossRefPubMedPubMedCentral

14.

Kim H, Choi P, Kim T, et al. Ginsenosides Rk1 and Rg5 inhibit transforming growth factor-β1-induced epithelial-mesenchymal transition and suppress migration, invasion, anoikis resistance, and development of stem-like features in lung cancer. J Ginseng Res. 2021;45(1):134–48. https://doi.org/10.1016/j.jgr.2020.02.005.CrossRefPubMed

15.

Ma Q, Yang L, Tolentino K, et al. Inducible lncRNA transgenic mice reveal continual role of HOTAIR in promoting breast cancer metastasis. Elife. 2022;11: e79126. https://doi.org/10.7554/eLife.79126.CrossRefPubMedPubMedCentral

16.

Liu M, Jia J, Wang X, et al. Long non-coding RNA HOTAIR promotes cervical cancer progression through regulating BCL2 via targeting miR-143–3p. Cancer Biol Ther. 2018;19(5):391–9.CrossRefPubMedPubMedCentral

17.

Cantile M, Di Bonito M, Bellis MTD, et al. Functional Interaction among lncRNA HOTAIR and MicroRNAs in cancer and other human diseases. Cancers. 2021;13(3):570. https://doi.org/10.3390/cancers13030570.CrossRefPubMedPubMedCentral

18.

Wang N, Jiang Y, Lv S, et al. HOTAIR expands the population of prostatic cancer stem-like cells and causes docetaxel resistance via activating STAT3 signaling. Aging. 2020;12(13):12771–82.CrossRefPubMedPubMedCentral

19.

Yang FL, Wei YX, Liao BY, et al. LncRNA HOTAIR regulates the expression of E-cadherin to affect nasopharyngeal carcinoma progression by recruiting histone methylase EZH2 to mediate H3K27 trimethylation. Genomics. 2021;113(4):2276–89. https://doi.org/10.1016/j.ygeno.2021.03.036.CrossRefPubMed

20.

Peng CL, Zhao XJ, Wei CC, et al. LncRNA HOTAIR promotes colon cancer development by down-regulating miRNA-34a. Eur Rev Med Pharmacol Sci. 2019;23(13):5752–61. https://doi.org/10.26355/eurrev_201907_18312.CrossRefPubMed

21.

Wang L, Yang F, Jia LT, et al. Missing links in epithelial-mesenchymal transition: long non-coding RNAs enter the arena. Cell Physiol Biochem. 2017;44(4):1665–80. https://doi.org/10.1159/000485766.CrossRefPubMed

22.

Bure IV, Nemtsova MV, Zaletaev DV. Roles of E-cadherin and noncoding RNAs in the epithelial–mesenchymal transition and progression in gastric cancer. Int J Mol Sci. 2019;20(12):2870. https://doi.org/10.3390/ijms2012287.CrossRefPubMedPubMedCentral

23.

Jaksik R, Drobna-Śledzińska M, Dawidowska M. RNA-seq library preparation for comprehensive transcriptome analysis in cancer cells: the impact of insert size. Genomics. 2021;113(6):4149–62. https://doi.org/10.1016/j.ygeno.2021.10.018.CrossRefPubMed

24.

Ura H, Togi S, Niida Y. A comparison of mRNA sequencing (RNA-Seq) library preparation methods for transcriptome analysis. BMC Genomics. 2022;23(1):303.CrossRefPubMedPubMedCentral

Title: LncRNA HOTAIR down-expression inhibits the invasion and tumorigenicity of epithelial ovarian cancer cells by suppressing TGF-β1 and ZEB1
Authors: Yufu Zhou
Yunjie Zhang
Yidan Shao
Xiaoli Yue
Yifan Chu
Cuiping Yang
Dengyu Chen
Publication date: 01-12-2023
Publisher: Springer US
Keywords: Ovarian Cancer
Ovarian Cancer
Published in: Discover Oncology / Issue 1/2023
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI: https://doi.org/10.1007/s12672-023-00846-5

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2023

A novel PD-1/PD-L1 pathway molecular typing-related signature for predicting prognosis and the tumor microenvironment in breast cancer

A gene signature predicting prognosis of patients with lower-grade gliomas receiving temozolomide therapy

PIK3CD correlates with prognosis, epithelial–mesenchymal transition and tumor immune infiltration in breast carcinoma

High pre-chemoradiotherapy pan-immune-inflammation value levels predict worse outcomes in patients with stage IIIB/C non-small-cell lung cancer

Systematic review and integrated analysis of prognostic gene signatures for prostate cancer patients

Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials