Long non‑coding nuclear paraspeckle assembly transcript 1 acts as prognosis biomarker and increases cell growth and invasion in cervical cancer by sequestering microRNA‑101

Wang,Li; Zhu,Hongying

doi:10.3892/mmr.2017.8186

Long non‑coding nuclear paraspeckle assembly transcript 1 acts as prognosis biomarker and increases cell growth and invasion in cervical cancer by sequestering microRNA‑101

Authors:
- Li Wang
- Hongying Zhu
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Affiliations: Department of Obstetrics and Gynecology, Xidian Group Hospital, Xi'an, Shaanxi 710077, P.R. China, Department of Obstetrics and Gynecology, Xianyang Caihong Hospital, Xianyang, Shaanxi 712021, P.R. China
Published online on: November 29, 2017 https://doi.org/10.3892/mmr.2017.8186
Pages: 2771-2777

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Abstract

Emerging studies have focused on the essential role of long non‑coding RNAs (lncRNAs) in cervical carcinogenesis. A recent study has indicated that nuclear paraspeckle assembly transcript 1 (NEAT1) is highly expressed in the human cervical tissue. However, whether NEAT1 is involved in cervical cancer remains to be elucidated. Reverse transcription‑quantitative polymerase chain reaction results demonstrated that the expression of NEAT1 was higher in cervical cancer cells/tissues compared with that in normal human keratinocytes/tissues. Patients with higher NEAT1 level had poorer clinical characteristics and a shorter survival time compared with those that exhibited lower NEAT1 expression levels. In vitro, flow cytometery analysis revealed that transfection with NEAT1 small interfering RNA retarded cervical cancer cell (Caski and HeLa) growth by decreasing the percentage of S phase in the cell cycle and inducing cell apoptosis. In addition, the colony formation assay, wound healing assay and matrigel invasion assay results indicated that downregulation of NEAT1 inhibited colony formation, cell migration and invasion. Further investigation using the luciferase reporter assay revealed that the expression of mircoRNA‑101 (miR‑101) target gene Fos was positively associated with NEAT1 expression due to NEAT1‑competitive molecular sequestering of miR‑101 via base pairing. Furthermore, reduction of miR‑101 expression by inhibitor transfection reversed the effect of NEAT1 siRNA on cervical cancer cells. To conclude, the present data indicated that NEAT1 promoted cervical cancer progression by targeting miR‑101.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Chen J, Fu Z, Ji C, Gu P, Xu P, Yu N, Kan Y, Wu X, Shen R and Shen Y: Systematic gene microarray analysis of the lncRNA expression profiles in human uterine cervix carcinoma. Biomed Pharmacother. 72:83–90. 2015. View Article : Google Scholar : PubMed/NCBI
3	Sakuragi N: Refining insight into cervical cancer progression. Lancet Oncol. 15:371–372. 2014. View Article : Google Scholar : PubMed/NCBI
4	Schiffman M, Wentzensen N, Wacholder S, Kinney W, Gage JC and Castle PE: Human papillomavirus testing in the prevention of cervical cancer. J Natl Cancer Inst. 103:368–383. 2011. View Article : Google Scholar : PubMed/NCBI
5	Baak JP, Kruse AJ, Robboy SJ, Janssen EA, van Diermen B and Skaland I: Dynamic behavioural interpretation of cervical intraepithelial neoplasia with molecular biomarkers. J Clin Pathol. 59:1017–1028. 2006. View Article : Google Scholar : PubMed/NCBI
6	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. View Article : Google Scholar : PubMed/NCBI
7	Mattick JS: The genetic signatures of noncoding RNAs. PLoS Genet. 5:e10004592009. View Article : Google Scholar : PubMed/NCBI
8	Gibb EA, Brown CJ and Lam WL: The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 10:382011. View Article : Google Scholar : PubMed/NCBI
9	Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: Insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI
10	Calore F, Lovat F and Garofalo M: Non-coding RNAs and cancer. Int J Mol Sci. 14:17085–17110. 2013. View Article : Google Scholar : PubMed/NCBI
11	Zhang J, Liu SC, Luo XH, Tao GX, Guan M, Yuan H and Hu DK: Exosomal long noncoding RNAs are differentially expressed in the cervicovaginal lavage samples of cervical cancer patients. J Clin Lab Anal. 30:1116–1121. 2016. View Article : Google Scholar : PubMed/NCBI
12	Gibb EA, Becker-Santos DD, Enfield KS, Guillaud M, Niekerk Dv, Matisic JP, Macaulay CE and Lam WL: Aberrant expression of long noncoding RNAs in cervical intraepithelial neoplasia. Int J Gynecol Cancer. 22:1557–1563. 2012. View Article : Google Scholar : PubMed/NCBI
13	Jen J, Tang YA, Lu YH, Lin CC, Lai WW and Wang YC: Oct4 transcriptionally regulates the expression of long non-coding RNAs NEAT1 and MALAT1 to promote lung cancer progression. Mol Cancer. 16:1042017. View Article : Google Scholar : PubMed/NCBI
14	Chen X, Kong J, Ma Z, Gao S and Feng X: Up regulation of the long non-coding RNA NEAT1 promotes esophageal squamous cell carcinoma cell progression and correlates with poor prognosis. Am J Cancer Res. 5:2808–2815. 2015. View Article : Google Scholar : PubMed/NCBI
15	Peng W, Wang Z and Fan H: LncRNA NEAT1 impacts cell proliferation and apoptosis of colorectal cancer via regulation of akt signaling. Pathol Oncol Res. 23:651–656. 2017. View Article : Google Scholar : PubMed/NCBI
16	Mang Y, Li L, Ran J, Zhang S, Liu J, Li L, Chen Y, Liu J, Gao Y and Ren G: Long noncoding RNA NEAT1 promotes cell proliferation and invasion by regulating hnRNP A2 expression in hepatocellular carcinoma cells. Onco Targets Ther. 10:1003–1016. 2017. View Article : Google Scholar : PubMed/NCBI
17	Ergun S and Oztuzcu S: Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways. Tumour Biol. 36:3129–3136. 2015. View Article : Google Scholar : PubMed/NCBI
18	Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, Chess A and Lawrence JB: An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell. 33:717–726. 2009. View Article : Google Scholar : PubMed/NCBI
19	Sasaki YT, Ideue T, Sano M, Mituyama T and Hirose T: MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proc Natl Acad Sci USA. 106:pp. 2525–2530. 2009; View Article : Google Scholar : PubMed/NCBI
20	Chen ZJ, Zhang Z, Xie BB and Zhang HY: Clinical significance of up-regulated lncRNA NEAT1 in prognosis of ovarian cancer. Eur Rev Med Pharmacol Sci. 20:3373–3377. 2016.PubMed/NCBI
21	Chakravarty D, Sboner A, Nair SS, Giannopoulou E, Li R, Hennig S, Mosquera JM, Pauwels J, Park K, Kossai M, et al: The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nat Commun. 5:53832014. View Article : Google Scholar : PubMed/NCBI
22	Fang J, Li Y, Zhang J, Yan M, Li J, Bao S and Jin T: Correlation between polymorphisms in microRNA-regulated genes and cervical cancer susceptibility in a Xinjiang Uygur population. Oncotarget. 8:31758–31764. 2017.PubMed/NCBI
23	Qian K, Liu G, Tang Z, Hu Y, Fang Y, Chen Z and Xu X: The long non-coding RNA NEAT1 interacted with miR-101 modulates breast cancer growth by targeting EZH2. Arch Biochem Biophys. 615:1–9. 2017. View Article : Google Scholar : PubMed/NCBI
24	Li JH, Zhang SQ, Qiu XG, Zhang SJ, Zheng SH and Zhang DH: Long non-coding RNA NEAT1 promotes malignant progression of thyroid carcinoma by regulating miRNA-214. Int J Oncol. 50:708–716. 2017. View Article : Google Scholar : PubMed/NCBI
25	Huang B, Liu C, Wu Q, Zhang J, Min Q, Sheng T, Wang X and Zou Y: Long non-coding RNA NEAT1 facilitates pancreatic cancer progression through negative modulation of miR-506-3p. Biochem Biophys Res Commun. 482:828–834. 2017. View Article : Google Scholar : PubMed/NCBI
26	Jiang R, Zhang C, Liu G, Gu R and Wu H: MicroRNA-101 inhibits proliferation, migration and invasion in osteosarcoma cells by targeting ROCK1. Am J Cancer Res. 7:88–97. 2017.PubMed/NCBI
27	Wang L, Yao J, Sun H, He K, Tong D, Song T and Huang C: MicroRNA-101 suppresses progression of lung cancer through the PTEN/AKT signaling pathway by targeting DNA methyltransferase 3A. Oncol Lett. 13:329–338. 2017.PubMed/NCBI
28	Liu J, Pang Y, Wang H, Li Y, Sun X, Xu F, Ren H and Liu D: miR-101 inhibits the proliferation and migration of breast cancer cells via downregulating the expression of DNA methyltransferase 3a. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 32:299–303. 2016.(In Chinese). PubMed/NCBI
29	Zheng HB, Zheng XG and Liu BP: miRNA-101 inhibits ovarian cancer cells proliferation and invasion by down-regulating expression of SOCS-2. Int J Clin Exp Med. 8:20263–20270. 2015.PubMed/NCBI
30	Huang F, Lin C, Shi YH and Kuerban G: MicroRNA-101 inhibits cell proliferation, invasion and promotes apoptosis by regulating cyclooxygenase-2 in Hela cervical carcinoma cells. Asian Pac J Cancer Prev. 14:5915–5920. 2013. View Article : Google Scholar : PubMed/NCBI
31	Liang X, Liu Y, Zeng L, Yu C, Hu Z, Zhou Q and Yang Z: miR-101 inhibits the G1-to-S phase transition of cervical cancer cells by targeting Fos. Int J Gynecol Cancer. 24:1165–1172. 2014. View Article : Google Scholar : PubMed/NCBI