Long non‑coding RNA HOTAIR overexpression improves premature ovarian failure by upregulating Notch‑1 expression

Zhao,Wei; Dong,Liwei

doi:10.3892/etm.2018.6750

Long non‑coding RNA HOTAIR overexpression improves premature ovarian failure by upregulating Notch‑1 expression

Authors:
- Wei Zhao
- Liwei Dong
View Affiliations

Affiliations: Department of Reproductive Medicine, People's Hospital of Dezhou, Dezhou, Shandong 253014, P.R. China
Published online on: September 17, 2018 https://doi.org/10.3892/etm.2018.6750
Pages: 4791-4795

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the role of long non‑coding (lnc)RNA HOTAIR in premature ovarian failure. A total of 69 women with spontaneous premature ovarian failure and 48 healthy women were enrolled in the present study. Ovarian tissues and blood samples were harvested from each participant. The expression of HOTAIR in ovarian tissues and sera was detected using reverse transcription‑quantitative polymerase chain reaction. A receiver operator characteristic curve analysis was performed to assess the diagnostic value of HOTAIR expression in ovarian tissues and sera for premature ovarian failure. Hamster ovary cell lines overexpressing HOTAIR were established and cell apoptosis were assessed using an MTT assay. The effect of HOTAIR upregulation on the expression of Notch‑1 was measured using western blotting. The expression of HOTAIR in ovarian tissues and serum samples was significantly lower in patients with premature ovarian failure compared with healthy controls. These results suggest that ovarian and serum HOTAIR expression levels may be used to accurately predict the risk of premature ovarian failure. It was also demonstrated that HOTAIR overexpression upregulates Notch‑1 protein expression in hamster ovary cells and reduced apoptosis, whereas the Notch inhibitor L685458 ameliorated these effects. In conclusion, the results of the present study suggest that LncRNA HOTAIR overexpression improves premature ovarian failure by upregulating the expression of Notch‑1.

View Figures

View References

1	Jankowska K: Premature ovarian failure. Prz Menopauzalny. 16:51–56. 2017.PubMed/NCBI
2	Kovanci E and Schutt AK: Premature ovarian failure: Clinical presentation and treatment. Obstet Gynecol Clin North Am. 42:153–161. 2015. View Article : Google Scholar : PubMed/NCBI
3	Silber SJ, Lenahan KM, Levine DJ, Pineda JA, Gorman KS, Friez MJ, Crawford EC and Gosden RG: Ovarian transplantation between monozygotic twins discordant for premature ovarian failure. N Engl J Med. 353:58–63. 2005. View Article : Google Scholar : PubMed/NCBI
4	Luisi S, Orlandini C, Regini C, Pizzo A, Vellucci F and Petraglia F: Premature ovarian insufficiency: From pathogenesis to clinical management. J Endocrinol Invest. 38:597–603. 2015. View Article : Google Scholar : PubMed/NCBI
5	Yang X, Gao L, Guo X, Shi X, Wu H, Song F and Wang B: A network based method for analysis of lncRNA-disease associations and prediction of lncRNAs implicated in diseases. PLoS One. 9:e877972014. View Article : Google Scholar : PubMed/NCBI
6	Cai B, Song XQ, Cai JP and Zhang S: HOTAIR: A cancer-related long non-coding RNA. Neoplasma. 61:379–391. 2014. View Article : Google Scholar : PubMed/NCBI
7	Xiong Y, Liu T, Wang S, Chi H, Chen C and Zheng J: Cyclophosphamide promotes the proliferation inhibition of mouse ovarian granulosa cells and premature ovarian failure by activating the lncRNA-Meg3-p53-p66Shc pathway. Gene. 596:1–8. 2017. View Article : Google Scholar : PubMed/NCBI
8	Qiu JJ, Lin YY, Ye LC, Ding JX, Feng WW, Jin HY, Zhang Y, Li Q and Hua KQ: Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer. Gynecol Oncol. 134:121–128. 2014. View Article : Google Scholar : PubMed/NCBI
9	Qiu JJ, Wang Y, Ding JX, Jin HY, Yang G and Hua KQ: The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis. Exp Cell Res. 333:238–248. 2015. View Article : Google Scholar : PubMed/NCBI
10	Cartwright B, Robinson J, Seed PT, Fogelman I and Rymer J: Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: A randomized controlled trial of the effects on bone mineral density. J Clin Endocrinol Metab. 101:3497–3505. 2016. View Article : Google Scholar : PubMed/NCBI
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
12	Dong C, Liu S, Lv Y, Zhang C, Gao H, Tan L and Wang H: Long non-coding RNA HOTAIR regulates proliferation and invasion via activating Notch signalling pathway in retinoblastoma. J Biosci. 41:677–687. 2016. View Article : Google Scholar : PubMed/NCBI
13	Liu TE, Wang S, Zhang L, Guo L, Yu Z, Chen C and Zheng J: Growth hormone treatment of premature ovarian failure in a mouse model via stimulation of the Notch-1 signaling pathway. Exp Ther Med. 12:215–221. 2016. View Article : Google Scholar : PubMed/NCBI
14	Yan J, Dang Y, Liu S, Zhang Y and Zhang G: LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes. Tumor Biol. 37:16345–16355. 2016. View Article : Google Scholar
15	Li H, An J, Wu M, Zheng Q, Gui X, Li T, Pu H and Lu D: LncRNA HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2. Oncotarget. 6:27847–27864. 2015.PubMed/NCBI
16	Teschendorff AE, Lee SH, Jones A, Fiegl H, Kalwa M, Wagner W, Chindera K, Evans I, Dubeau L, Orjalo A, et al: HOTAIR and its surrogate DNA methylation signature indicate carboplatin resistance in ovarian cancer. Genome Med. 7:1082015. View Article : Google Scholar : PubMed/NCBI
17	Pankla R, Buddhisa S, Berry M, Blankenship DM, Bancroft GJ, Banchereau J, Lertmemongkolchai G and Chaussabel D: Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis. Genome Biol. 10:R1272009. View Article : Google Scholar : PubMed/NCBI
18	Lin PY, Huang FJ, Kung FT, Chiang HJ, Lin YJ, Lin YC and Lan KC: Evaluation of serum anti-mullerian hormone as a biomarker of early ovarian aging in young women undergoing IVF/ICSI cycle. Int J Clin Exp Pathol. 7:6245–6253. 2014.PubMed/NCBI
19	Lee M, Kim HJ, Kim SW, Park SA, Chun KH, Cho NH, Song YS and Kim YT: The long non-coding RNA HOTAIR increases tumour growth and invasion in cervical cancer by targeting the Notch pathway. Oncotarget. 7:44558–44571. 2016.PubMed/NCBI
20	Shelly LL, Fuchs C and Miele L: Notch-1 inhibits apoptosis in murine erythroleukemia cells and is necessary for differentiation induced by hybrid polar compounds. J Cell Biochem. 73:164–175. 1999. View Article : Google Scholar : PubMed/NCBI
21	Wang Z, Zhang Y, Li Y, Banerjee S, Liao J and Sarkar FH: Down-regulation of Notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells. Mol Cancer Ther. 5:483–493. 2006. View Article : Google Scholar : PubMed/NCBI