Skip to main content
Top
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Cervical Cancer | Primary research

Up-regulated lncRNA XIST contributes to progression of cervical cancer via regulating miR-140-5p and ORC1

Authors: Xing Chen, Dongsheng Xiong, Liya Ye, Kai Wang, Lingfei Huang, Shuangshuang Mei, Jinhong Wu, Shanshan Chen, Xiaoli Lai, Lingzhi Zheng, Meifen Wang

Published in: Cancer Cell International | Issue 1/2019

Login to get access

Abstract

Background

The study purpose was to make investigation into the influence of XIST on cervical cancer progression and what’s more its potential mechanism.

Methods

The cervical cancer data sets (lncRNA, miRNA, and mRNA) obtained from TCGA were analyzed with the “mixOmics” R package. Then, the expression of XIST, miR-140-5p, and ORC1 were detected using qRT-PCR and western blot in both tissues and cervical cancer cell lines (Hela and C33A) to verify the bioinformatics analyses results. CCK-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) assays, cell cycle assay and cell apoptosis assay were practiced. Besides, immunohistochemistry staining was operated for the detection of the Ki-67, E-cadherin and vimentin expression in cervical cancer tissues and the apoptosis-related proteins expression (c-caspase3, Bcl-2, total PARP and cleaved PARP) was verified through western blot. And in vivo experiments were implemented.

Results

MiR-140-5p was down-regulated but XIST and ORC1 were up-regulated in cervical cancer tissues and cell lines. Knocking down of the XIST or ORC1 memorably suppressed cell proliferation, blocked cell cycle, decreased the expression of Bcl-2 while increased the apoptosis rate and the expression of c-caspase3 and cleaved PARP in HeLa and C33A cells. Besides, the results of immunohistochemistry staining showed knocking down the expression of XIST improved the expression levels of E-cadherin and decreased Ki-67 and vimentin expression. And overexpression of miR-140-5p also could inhibit the progression and reverse the influence of XIST and ORC1 in HeLa and C33A cells.

Conclusion

Our study indicated the effects of XIST/miR-140-5p/ORC1 axis on the progression of cervical cancer which will shed new light on epigenetic diagnostics and therapeutics in cervical cancer.
Literature
1.
go back to reference Shrestha AD, Neupane D, Vedsted P, Kallestrup P. Cervical cancer prevalence, incidence and mortality in low and middle income countries: a systematic review. Asian Pac J Cancer Prev. 2018;19:319–24.PubMedCentralPubMed Shrestha AD, Neupane D, Vedsted P, Kallestrup P. Cervical cancer prevalence, incidence and mortality in low and middle income countries: a systematic review. Asian Pac J Cancer Prev. 2018;19:319–24.PubMedCentralPubMed
2.
go back to reference Derks M, van der Velden J, de Kroon CD, Nijman HW, van Lonkhuijzen L, van der Zee AGJ, et al. Surgical treatment of early-stage cervical cancer: a multi-institution experience in 2124 cases in The Netherlands over a 30-year period. Int J Gynecol Cancer. 2018;28:757–63.CrossRefPubMed Derks M, van der Velden J, de Kroon CD, Nijman HW, van Lonkhuijzen L, van der Zee AGJ, et al. Surgical treatment of early-stage cervical cancer: a multi-institution experience in 2124 cases in The Netherlands over a 30-year period. Int J Gynecol Cancer. 2018;28:757–63.CrossRefPubMed
3.
go back to reference Meijer CJ, Snijders PJ. Cervical cancer in 2013: screening comes of age and treatment progress continues. Nat Rev Clin Oncol. 2014;11:77–8.CrossRefPubMed Meijer CJ, Snijders PJ. Cervical cancer in 2013: screening comes of age and treatment progress continues. Nat Rev Clin Oncol. 2014;11:77–8.CrossRefPubMed
4.
go back to reference Tang Y, He R, An J, Deng P, Huang L, Yang W. lncRNA XIST interacts with miR-140 to modulate lung cancer growth by targeting iASPP. Oncol Rep. 2017;38:941–8.CrossRefPubMed Tang Y, He R, An J, Deng P, Huang L, Yang W. lncRNA XIST interacts with miR-140 to modulate lung cancer growth by targeting iASPP. Oncol Rep. 2017;38:941–8.CrossRefPubMed
5.
go back to reference Rohart F, Gautier B, Singh A, Le Cao KA. mixOmics: an R package for ‘omics feature selection and multiple data integration. PLoS Comput Biol. 2017;13:e1005752.CrossRefPubMedPubMedCentral Rohart F, Gautier B, Singh A, Le Cao KA. mixOmics: an R package for ‘omics feature selection and multiple data integration. PLoS Comput Biol. 2017;13:e1005752.CrossRefPubMedPubMedCentral
7.
go back to reference Liang H, Zhang C, Guan H, Liu J, Cui Y. LncRNA DANCR promotes cervical cancer progression by upregulating ROCK1 via sponging miR-335-5p. J Cell Physiol. 2018;234(5):7266–78.CrossRefPubMed Liang H, Zhang C, Guan H, Liu J, Cui Y. LncRNA DANCR promotes cervical cancer progression by upregulating ROCK1 via sponging miR-335-5p. J Cell Physiol. 2018;234(5):7266–78.CrossRefPubMed
8.
go back to reference Guo H, Yang S, Li S, Yan M, Li L, Zhang H. LncRNA SNHG20 promotes cell proliferation and invasion via miR-140-5p-ADAM10 axis in cervical cancer. Biomed Pharmacother. 2018;102:749–57.CrossRefPubMed Guo H, Yang S, Li S, Yan M, Li L, Zhang H. LncRNA SNHG20 promotes cell proliferation and invasion via miR-140-5p-ADAM10 axis in cervical cancer. Biomed Pharmacother. 2018;102:749–57.CrossRefPubMed
9.
go back to reference Zhang Y, Cheng X, Liang H, Jin Z. Long non-coding RNA HOTAIR and STAT3 synergistically regulate the cervical cancer cell migration and invasion. Chem Biol Interact. 2018;286:106–10.CrossRefPubMed Zhang Y, Cheng X, Liang H, Jin Z. Long non-coding RNA HOTAIR and STAT3 synergistically regulate the cervical cancer cell migration and invasion. Chem Biol Interact. 2018;286:106–10.CrossRefPubMed
10.
go back to reference Peng J, Hou F, Feng J, Xu SX, Meng XY. Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 in vitro and in vivo. Oncol Lett. 2018;15:5809–18.PubMedCentralPubMed Peng J, Hou F, Feng J, Xu SX, Meng XY. Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 in vitro and in vivo. Oncol Lett. 2018;15:5809–18.PubMedCentralPubMed
11.
go back to reference Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991;349:38–44.CrossRefPubMed Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991;349:38–44.CrossRefPubMed
13.
go back to reference Zheng R, Lin S, Guan L, Yuan H, Liu K, Liu C, et al. Long non-coding RNA XIST inhibited breast cancer cell growth, migration, and invasion via miR-155/CDX1 axis. Biochem Biophys Res Commun. 2018;498:1002–8.CrossRefPubMed Zheng R, Lin S, Guan L, Yuan H, Liu K, Liu C, et al. Long non-coding RNA XIST inhibited breast cancer cell growth, migration, and invasion via miR-155/CDX1 axis. Biochem Biophys Res Commun. 2018;498:1002–8.CrossRefPubMed
14.
go back to reference Liu X, Cui L, Hua D. Long non-coding RNA XIST regulates miR-137-EZH2 axis to promote tumor metastasis in colorectal cancer. Oncol Res. 2018;27(1):99–106.CrossRefPubMedPubMedCentral Liu X, Cui L, Hua D. Long non-coding RNA XIST regulates miR-137-EZH2 axis to promote tumor metastasis in colorectal cancer. Oncol Res. 2018;27(1):99–106.CrossRefPubMedPubMedCentral
15.
go back to reference Sun Z, Zhang B, Cui T. Long non-coding RNA XIST exerts oncogenic functions in pancreatic cancer via miR-34a-5p. Oncol Rep. 2018;39:1591–600.PubMedCentralPubMed Sun Z, Zhang B, Cui T. Long non-coding RNA XIST exerts oncogenic functions in pancreatic cancer via miR-34a-5p. Oncol Rep. 2018;39:1591–600.PubMedCentralPubMed
16.
go back to reference Kobayashi R, Miyagawa R, Yamashita H, Morikawa T, Okuma K, Fukayama M, et al. Increased expression of long non-coding RNA XIST predicts favorable prognosis of cervical squamous cell carcinoma subsequent to definitive chemoradiation therapy. Oncol Lett. 2016;12:3066–74.CrossRefPubMedPubMedCentral Kobayashi R, Miyagawa R, Yamashita H, Morikawa T, Okuma K, Fukayama M, et al. Increased expression of long non-coding RNA XIST predicts favorable prognosis of cervical squamous cell carcinoma subsequent to definitive chemoradiation therapy. Oncol Lett. 2016;12:3066–74.CrossRefPubMedPubMedCentral
17.
go back to reference Wang W, Liu Y, Guo J, et al. miR-100 maintains phenotype of tumor-associated macrophages by targeting mTOR to promote tumor metastasis via Stat5a/IL-1ra pathway in mouse breast cancer. Oncogenesis. 2018;7(12):97.CrossRefPubMedPubMedCentral Wang W, Liu Y, Guo J, et al. miR-100 maintains phenotype of tumor-associated macrophages by targeting mTOR to promote tumor metastasis via Stat5a/IL-1ra pathway in mouse breast cancer. Oncogenesis. 2018;7(12):97.CrossRefPubMedPubMedCentral
19.
go back to reference Poudyal D, Herman A, Adelsberger JW, Yang J, Hu X, Chen Q, et al. A novel microRNA, hsa-miR-6852 differentially regulated by Interleukin-27 induces necrosis in cervical cancer cells by downregulating the FoxM1 expression. Sci Rep. 2018;8:900.CrossRefPubMedPubMedCentral Poudyal D, Herman A, Adelsberger JW, Yang J, Hu X, Chen Q, et al. A novel microRNA, hsa-miR-6852 differentially regulated by Interleukin-27 induces necrosis in cervical cancer cells by downregulating the FoxM1 expression. Sci Rep. 2018;8:900.CrossRefPubMedPubMedCentral
20.
go back to reference Su Y, Xiong J, Hu J, Wei X, Zhang X, Rao L. MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis. Oncotarget. 2016;7:68397–411.PubMedCentralPubMed Su Y, Xiong J, Hu J, Wei X, Zhang X, Rao L. MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis. Oncotarget. 2016;7:68397–411.PubMedCentralPubMed
21.
go back to reference Liang S, Gong X, Zhang G, Huang G, Lu Y, Li Y. The lncRNA XIST interacts with miR-140/miR-124/iASPP axis to promote pancreatic carcinoma growth. Oncotarget. 2017;8:113701–18.PubMedCentralPubMed Liang S, Gong X, Zhang G, Huang G, Lu Y, Li Y. The lncRNA XIST interacts with miR-140/miR-124/iASPP axis to promote pancreatic carcinoma growth. Oncotarget. 2017;8:113701–18.PubMedCentralPubMed
22.
go back to reference Kara N, Hossain M, Prasanth SG, Stillman B. Orc1 binding to mitotic chromosomes precedes spatial patterning during G1 phase and assembly of the origin recognition complex in human cells. J Biol Chem. 2015;290:12355–69.CrossRefPubMedPubMedCentral Kara N, Hossain M, Prasanth SG, Stillman B. Orc1 binding to mitotic chromosomes precedes spatial patterning during G1 phase and assembly of the origin recognition complex in human cells. J Biol Chem. 2015;290:12355–69.CrossRefPubMedPubMedCentral
23.
go back to reference Shu MQ, Qin YL, Jiang MH. RNA interference targeting ORC1 gene suppresses the proliferation of vascular smooth muscle cells in rats. Exp Mol Pathol. 2008;84:206–12.CrossRefPubMed Shu MQ, Qin YL, Jiang MH. RNA interference targeting ORC1 gene suppresses the proliferation of vascular smooth muscle cells in rats. Exp Mol Pathol. 2008;84:206–12.CrossRefPubMed
24.
go back to reference Peng W, Si S, Zhang Q, Li C, Zhao F, Wang F, et al. Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression. J Exp Clin Cancer Res. 2015;34:79.CrossRefPubMedPubMedCentral Peng W, Si S, Zhang Q, Li C, Zhao F, Wang F, et al. Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression. J Exp Clin Cancer Res. 2015;34:79.CrossRefPubMedPubMedCentral
25.
go back to reference Zhu H, Zheng T, Yu J, Zhou L, Wang L. LncRNA XIST accelerates cervical cancer progression via upregulating Fus through competitively binding with miR-200a. Biomed Pharmacother. 2018;105:789–97.CrossRefPubMed Zhu H, Zheng T, Yu J, Zhou L, Wang L. LncRNA XIST accelerates cervical cancer progression via upregulating Fus through competitively binding with miR-200a. Biomed Pharmacother. 2018;105:789–97.CrossRefPubMed
26.
go back to reference Masferrer E, Ferrandiz-Pulido C, Masferrer-Niubo M, Rodriguez-Rodriguez A, Gil I, Pont A, et al. Epithelial-to-mesenchymal transition in penile squamous cell carcinoma. J Urol. 2015;193:699–705.CrossRefPubMed Masferrer E, Ferrandiz-Pulido C, Masferrer-Niubo M, Rodriguez-Rodriguez A, Gil I, Pont A, et al. Epithelial-to-mesenchymal transition in penile squamous cell carcinoma. J Urol. 2015;193:699–705.CrossRefPubMed
27.
go back to reference Ren Z, Yang T, Zhang P, Liu K, Liu W, Wang P. SKA2 mediates invasion and metastasis in human breast cancer via EMT. Mol Med Rep. 2018;19(1):515–23.PubMed Ren Z, Yang T, Zhang P, Liu K, Liu W, Wang P. SKA2 mediates invasion and metastasis in human breast cancer via EMT. Mol Med Rep. 2018;19(1):515–23.PubMed
28.
go back to reference Odero-Marah V, Hawsawi O, Henderson V, Sweeney J. Epithelial–mesenchymal transition (EMT) and prostate cancer. Adv Exp Med Biol. 2018;1095:101–10.CrossRefPubMed Odero-Marah V, Hawsawi O, Henderson V, Sweeney J. Epithelial–mesenchymal transition (EMT) and prostate cancer. Adv Exp Med Biol. 2018;1095:101–10.CrossRefPubMed
29.
go back to reference Xu R, Zhu X, Chen F, Huang C, Ai K, Wu H, et al. LncRNA XIST/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells. Cancer Cell Int. 2018;18:41.CrossRefPubMedPubMedCentral Xu R, Zhu X, Chen F, Huang C, Ai K, Wu H, et al. LncRNA XIST/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells. Cancer Cell Int. 2018;18:41.CrossRefPubMedPubMedCentral
30.
go back to reference Zhang Y, Xu Y, Feng L, Li F, Sun Z, Wu T, et al. Comprehensive characterization of lncRNA-mRNA related ceRNA network across 12 major cancers. Oncotarget. 2016;7:64148–67.PubMedCentralPubMed Zhang Y, Xu Y, Feng L, Li F, Sun Z, Wu T, et al. Comprehensive characterization of lncRNA-mRNA related ceRNA network across 12 major cancers. Oncotarget. 2016;7:64148–67.PubMedCentralPubMed
33.
go back to reference Dong P, Xiong Y, Yu J, Chen L, Tao T, Yi S, et al. Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4-miR-18a pathway in cervical cancer. Oncogene. 2018;37:5257–68.CrossRefPubMedPubMedCentral Dong P, Xiong Y, Yu J, Chen L, Tao T, Yi S, et al. Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4-miR-18a pathway in cervical cancer. Oncogene. 2018;37:5257–68.CrossRefPubMedPubMedCentral
34.
go back to reference Yao S, Xu J, Zhao K, Song P, Yan Q, Fan W, et al. Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways. Cell Death Dis. 2018;9:1055.CrossRefPubMedPubMedCentral Yao S, Xu J, Zhao K, Song P, Yan Q, Fan W, et al. Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways. Cell Death Dis. 2018;9:1055.CrossRefPubMedPubMedCentral
35.
36.
go back to reference Wang X, Li L, Liang Y, Li C, Zhao H, Ye D, et al. Targeting the neddylation pathway to suppress the growth of prostate cancer cells: therapeutic implication for the men’s cancer. Biomed Res Int. 2014;2014:974309.PubMedCentralPubMed Wang X, Li L, Liang Y, Li C, Zhao H, Ye D, et al. Targeting the neddylation pathway to suppress the growth of prostate cancer cells: therapeutic implication for the men’s cancer. Biomed Res Int. 2014;2014:974309.PubMedCentralPubMed
Metadata
Title
Up-regulated lncRNA XIST contributes to progression of cervical cancer via regulating miR-140-5p and ORC1
Authors
Xing Chen
Dongsheng Xiong
Liya Ye
Kai Wang
Lingfei Huang
Shuangshuang Mei
Jinhong Wu
Shanshan Chen
Xiaoli Lai
Lingzhi Zheng
Meifen Wang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0744-y

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine