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Erschienen in: Cancer Chemotherapy and Pharmacology 3/2016

01.03.2016 | Original Article

Long noncoding RNA HOTAIR is a prognostic biomarker and inhibits chemosensitivity to doxorubicin in bladder transitional cell carcinoma

verfasst von: Chao Shang, Yan Guo, Hui Zhang, Yi-xue Xue

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2016

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Abstract

Purpose

In this study, whether HOTAIR is a prognostic biomarker will be detected, and its regulative effects of chemosensitivity to doxorubicin in TCC cells will be examined.

Methods

The expression of HOTAIR was detected by quantitative real-time PCR. Overall survival rate was calculated by Kaplan–Meier method with the log-rank test for comparisons. MTT assay was used to detect cell proliferation ability and chemosensitivity. Dual-color flow cytometric method was used to detect cell apoptosis.

Results

HOTAIR was up-regulated in bladder transitional cell carcinoma (TCC) tissues and cell lines compared with normal bladder transitional cell (NBTC) tissues and bladder epithelial immortalized SV-HUC-1 cells, and its expression level had positive correlation with histological grades of TCC. Moreover, HOTAIR was an independent prognostic biomarker of overall survival for TCC patients. The expression and silence vector for HOTAIR were transfected into T24 and J82 cells to up-regulate and silence the HOTAIR expression, respectively. In T24 and J82 cells, HOTAIR over-expression promoted cell proliferation and inhibited chemosensitivity to doxorubicin and cell apoptosis induced by doxorubicin; silence of HOTAIR showed opposite regulative effects.

Conclusions

In summary, lncRNA HOTAIR was an independent prognostic biomarker of overall survival in TCC patients and could regulate chemosensitivity to doxorubicin of human TCC cells. HOTAIR might provide a new potential therapeutic target and stratagem for TCC.
Literatur
1.
Zurück zum Zitat Murta-Nascimento C, Schmitz-Dräger BJ, Zeegers MP, Steineck G, Kogevinas M, Real FX, Malats N (2007) Epidemiology of urinary bladder cancer: from tumor development to patient’s death. World J Urol 25:285–295CrossRefPubMed Murta-Nascimento C, Schmitz-Dräger BJ, Zeegers MP, Steineck G, Kogevinas M, Real FX, Malats N (2007) Epidemiology of urinary bladder cancer: from tumor development to patient’s death. World J Urol 25:285–295CrossRefPubMed
2.
Zurück zum Zitat Hassen W, Droller MJ (2000) Current concepts in assessment and treatment of bladder cancer. Curr Opin Urol 10:291–299CrossRefPubMed Hassen W, Droller MJ (2000) Current concepts in assessment and treatment of bladder cancer. Curr Opin Urol 10:291–299CrossRefPubMed
3.
Zurück zum Zitat Xu XD, Li KR, Li XM, Yao J, Qin J, Yan B (2014) Long non-coding RNAs: new players in ocular neovascularization. Mol Biol Rep 41(7):4493–4505CrossRefPubMed Xu XD, Li KR, Li XM, Yao J, Qin J, Yan B (2014) Long non-coding RNAs: new players in ocular neovascularization. Mol Biol Rep 41(7):4493–4505CrossRefPubMed
4.
Zurück zum Zitat Zhao Y, Feng G, Wang Y, Yue Y, Zhao W (2014) Regulation of apoptosis by long non-coding RNA HIF1A-AS1 in VSMCs: implications for TAA pathogenesis. Int J Clin Exp Pathol 7(11):7643–7652PubMedCentralPubMed Zhao Y, Feng G, Wang Y, Yue Y, Zhao W (2014) Regulation of apoptosis by long non-coding RNA HIF1A-AS1 in VSMCs: implications for TAA pathogenesis. Int J Clin Exp Pathol 7(11):7643–7652PubMedCentralPubMed
5.
Zurück zum Zitat Song J, Ahn C, Chun CH, Jin EJ (2014) A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis. J Orthop Res 32(12):1628–1635CrossRefPubMed Song J, Ahn C, Chun CH, Jin EJ (2014) A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis. J Orthop Res 32(12):1628–1635CrossRefPubMed
6.
Zurück zum Zitat Modali SD, Parekh VI, Kebebew E, Agarwal SK (2015) Epigenetic regulation of the lncRNA MEG3 and its target c-MET in pancreatic neuroendocrine tumors. Mol Endocrinol 29(2):224–237PubMedCentralCrossRefPubMed Modali SD, Parekh VI, Kebebew E, Agarwal SK (2015) Epigenetic regulation of the lncRNA MEG3 and its target c-MET in pancreatic neuroendocrine tumors. Mol Endocrinol 29(2):224–237PubMedCentralCrossRefPubMed
7.
Zurück zum Zitat Wang X, Li M, Wang Z, Han S, Tang X, Ge Y, Zhou L, Zhou C, Yuan Q, Yang M (2015) Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217inhibits proliferation, migration and invasion of esophageal squamous cell carcinoma cells. J Biol Chem 290(7):3925–3935PubMedCentralCrossRefPubMed Wang X, Li M, Wang Z, Han S, Tang X, Ge Y, Zhou L, Zhou C, Yuan Q, Yang M (2015) Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217inhibits proliferation, migration and invasion of esophageal squamous cell carcinoma cells. J Biol Chem 290(7):3925–3935PubMedCentralCrossRefPubMed
8.
Zurück zum Zitat Song B, Guan Z, Liu F, Sun D, Wang K, Qu H (2015) Long non-coding RNA HOTAIR promotes HLA-G expression via inhibiting miR-152 in gastric cancer cells. Biochem Biophys Res Commun 464(3):807–813CrossRefPubMed Song B, Guan Z, Liu F, Sun D, Wang K, Qu H (2015) Long non-coding RNA HOTAIR promotes HLA-G expression via inhibiting miR-152 in gastric cancer cells. Biochem Biophys Res Commun 464(3):807–813CrossRefPubMed
9.
Zurück zum Zitat Li H, An J, Wu M, Zheng Q, Gui X, Li T, Pu H, Lu D (2015) LncRNA HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2. Oncotarget 6(29):27847–27864PubMedCentralCrossRefPubMed Li H, An J, Wu M, Zheng Q, Gui X, Li T, Pu H, Lu D (2015) LncRNA HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2. Oncotarget 6(29):27847–27864PubMedCentralCrossRefPubMed
10.
Zurück zum Zitat Yan TH, Lu SW, Huang YQ, Que GB, Chen JH, Chen YP, Zhang HB, Liang XL, Jiang JH (2014) Upregulation of the long noncoding RNA HOTAIR predicts recurrence in stage Ta/T1 bladdercancer. Tumour Biol 35(10):10249–10257CrossRefPubMed Yan TH, Lu SW, Huang YQ, Que GB, Chen JH, Chen YP, Zhang HB, Liang XL, Jiang JH (2014) Upregulation of the long noncoding RNA HOTAIR predicts recurrence in stage Ta/T1 bladdercancer. Tumour Biol 35(10):10249–10257CrossRefPubMed
11.
Zurück zum Zitat Ke J, Yao YL, Zheng J, Wang P, Liu YH, Ma J, Li Z, Liu XB, Li ZQ, Wang ZH, Xue YX (2015) Knockdown of long non-coding RNA HOTAIR inhibits malignant biological behaviors of human glioma cells via modulation of miR-326. Oncotarget 6(26):21934–21949PubMedCentralCrossRefPubMed Ke J, Yao YL, Zheng J, Wang P, Liu YH, Ma J, Li Z, Liu XB, Li ZQ, Wang ZH, Xue YX (2015) Knockdown of long non-coding RNA HOTAIR inhibits malignant biological behaviors of human glioma cells via modulation of miR-326. Oncotarget 6(26):21934–21949PubMedCentralCrossRefPubMed
12.
Zurück zum Zitat Shang C, Guo Y, Hong Y, Liu YH, Xue YX (2015) MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and proliferation by targeting FASLG. Mol Biol Rep 42(3):721–727CrossRefPubMed Shang C, Guo Y, Hong Y, Liu YH, Xue YX (2015) MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and proliferation by targeting FASLG. Mol Biol Rep 42(3):721–727CrossRefPubMed
13.
Zurück zum Zitat Alaimo S, Giugno R, Pulvirenti A (2014) ncPred: ncRNA-disease association prediction through tripartite network-based inference. Front Bioeng Biotechnol 2:71PubMedCentralCrossRefPubMed Alaimo S, Giugno R, Pulvirenti A (2014) ncPred: ncRNA-disease association prediction through tripartite network-based inference. Front Bioeng Biotechnol 2:71PubMedCentralCrossRefPubMed
14.
Zurück zum Zitat Fang TT, Sun XJ, Chen J, Zhao Y, Sun RX, Ren N, Liu BB (2014) Long non-coding RNAs are differentially expressed in hepatocellular carcinoma cell lines with differing metastatic potential. Asian Pac J Cancer Prev 15(23):10513–10524CrossRefPubMed Fang TT, Sun XJ, Chen J, Zhao Y, Sun RX, Ren N, Liu BB (2014) Long non-coding RNAs are differentially expressed in hepatocellular carcinoma cell lines with differing metastatic potential. Asian Pac J Cancer Prev 15(23):10513–10524CrossRefPubMed
15.
Zurück zum Zitat Nie F, Sun M, Yang J, Xie M, Xu TP, Xia R, Liu YW, Liu XH, Zhang EB, Lu KH, Shu YQ (2015) Long noncoding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther 14(1):268–277CrossRefPubMed Nie F, Sun M, Yang J, Xie M, Xu TP, Xia R, Liu YW, Liu XH, Zhang EB, Lu KH, Shu YQ (2015) Long noncoding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther 14(1):268–277CrossRefPubMed
16.
Zurück zum Zitat Wang Y, Liu X, Zhang H, Sun L, Zhou Y, Jin H, Zhang H, Zhang H, Liu J, Guo H, Nie Y, Wu K, Fan D, Zhang H, Liu L (2014) Hypoxia-inducible lncRNA-AK058003 promotes gastric cancer metastasis by targeting γ-synuclein. Neoplasia 16(12):1094–1106PubMedCentralCrossRefPubMed Wang Y, Liu X, Zhang H, Sun L, Zhou Y, Jin H, Zhang H, Zhang H, Liu J, Guo H, Nie Y, Wu K, Fan D, Zhang H, Liu L (2014) Hypoxia-inducible lncRNA-AK058003 promotes gastric cancer metastasis by targeting γ-synuclein. Neoplasia 16(12):1094–1106PubMedCentralCrossRefPubMed
17.
Zurück zum Zitat Wang Y, Guo Q, Zhao Y, Chen J, Wang S, Hu J, Sun Y (2014) BRAF-activated long non-coding RNA contributes to cell proliferation and activates autophagy in papillary thyroid carcinoma. Oncol Lett 8(5):1947–1952PubMedCentralPubMed Wang Y, Guo Q, Zhao Y, Chen J, Wang S, Hu J, Sun Y (2014) BRAF-activated long non-coding RNA contributes to cell proliferation and activates autophagy in papillary thyroid carcinoma. Oncol Lett 8(5):1947–1952PubMedCentralPubMed
18.
Zurück zum Zitat Banet G, Bibi O, Matouk I, Ayesh S, Laster M, Kimber KM, Tykocinski M, de Groot N, Hochberg A, Ohana P (2000) Characterization of human and mouse H19 regulatory sequences. Mol Biol Rep 27(3):157–165CrossRefPubMed Banet G, Bibi O, Matouk I, Ayesh S, Laster M, Kimber KM, Tykocinski M, de Groot N, Hochberg A, Ohana P (2000) Characterization of human and mouse H19 regulatory sequences. Mol Biol Rep 27(3):157–165CrossRefPubMed
19.
Zurück zum Zitat Kraus TF, Greiner A, Guibourt V, Lisec K, Kretzschmar HA (2015) Identification of stably expressed lncRNAs as valid endogenous controls for profiling of human glioma. J Cancer 6(2):111–119PubMedCentralCrossRefPubMed Kraus TF, Greiner A, Guibourt V, Lisec K, Kretzschmar HA (2015) Identification of stably expressed lncRNAs as valid endogenous controls for profiling of human glioma. J Cancer 6(2):111–119PubMedCentralCrossRefPubMed
20.
Zurück zum Zitat Wang HM, Lu JH, Chen WY, Gu AQ (2015) Upregulated lncRNA-UCA1 contributes to progression of lung cancer and is closely related to clinical diagnosis as a predictive biomarker in plasma. Int J Clin Exp Med 8(7):11824–11830PubMedCentralPubMed Wang HM, Lu JH, Chen WY, Gu AQ (2015) Upregulated lncRNA-UCA1 contributes to progression of lung cancer and is closely related to clinical diagnosis as a predictive biomarker in plasma. Int J Clin Exp Med 8(7):11824–11830PubMedCentralPubMed
21.
Zurück zum Zitat Zhi F, Wang Q, Xue L, Shao N, Wang R, Deng D, Wang S, Xia X, Yang Y (2015) The use of three long non-coding RNAs as potential prognostic biomarkers of astrocytoma. PLoS One 10(8):e0135242PubMedCentralCrossRefPubMed Zhi F, Wang Q, Xue L, Shao N, Wang R, Deng D, Wang S, Xia X, Yang Y (2015) The use of three long non-coding RNAs as potential prognostic biomarkers of astrocytoma. PLoS One 10(8):e0135242PubMedCentralCrossRefPubMed
22.
Zurück zum Zitat Zhao XL, Zhao ZH, Xu WC, Hou JQ, Du XY (2015) Increased expression of SPRY4-IT1 predicts poor prognosis and promotes tumor growth and metastasis in bladder cancer. Int J Clin Exp Pathol 8(2):1954–1960PubMedCentralPubMed Zhao XL, Zhao ZH, Xu WC, Hou JQ, Du XY (2015) Increased expression of SPRY4-IT1 predicts poor prognosis and promotes tumor growth and metastasis in bladder cancer. Int J Clin Exp Pathol 8(2):1954–1960PubMedCentralPubMed
23.
Zurück zum Zitat Zhao W, Dong S, Duan B, Chen P, Shi L, Gao H, Qi H (2015) HOTAIR is a predictive and prognostic biomarker for patients with advanced gastric adenocarcinoma receiving fluorouracil and platinum combination chemotherapy. Am J Transl Res 7(7):1295–1302PubMedCentralPubMed Zhao W, Dong S, Duan B, Chen P, Shi L, Gao H, Qi H (2015) HOTAIR is a predictive and prognostic biomarker for patients with advanced gastric adenocarcinoma receiving fluorouracil and platinum combination chemotherapy. Am J Transl Res 7(7):1295–1302PubMedCentralPubMed
24.
Zurück zum Zitat Zhang JX, Han L, Bao ZS, Wang YY, Chen LY, Yan W, Yu SZ, Pu PY, Liu N, You YP, Jiang T, Kang CS, Chinese Glioma Cooperative Group (2013) HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma. Neuro Oncol 15(12):1595–1603PubMedCentralCrossRefPubMed Zhang JX, Han L, Bao ZS, Wang YY, Chen LY, Yan W, Yu SZ, Pu PY, Liu N, You YP, Jiang T, Kang CS, Chinese Glioma Cooperative Group (2013) HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma. Neuro Oncol 15(12):1595–1603PubMedCentralCrossRefPubMed
25.
Zurück zum Zitat Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncodingRNAs. Cell 129(7):1311–1323PubMedCentralCrossRefPubMed Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncodingRNAs. Cell 129(7):1311–1323PubMedCentralCrossRefPubMed
26.
Zurück zum Zitat Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, Fujiya T, Sato I, Yamaguchi K, Tanaka N, Iijima K, Shimosegawa T, Sugamura K, Satoh K (2013) Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PLoS One 8(10):e77070PubMedCentralCrossRefPubMed Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, Fujiya T, Sato I, Yamaguchi K, Tanaka N, Iijima K, Shimosegawa T, Sugamura K, Satoh K (2013) Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PLoS One 8(10):e77070PubMedCentralCrossRefPubMed
27.
Zurück zum Zitat Hong Y, Shang C, Xue YX, Liu YH (2015) Silencing of Bmi-1 gene enhances chemotherapy sensitivity in human glioblastoma cells. Med Sci Monit 21:1002–1007PubMedCentralCrossRefPubMed Hong Y, Shang C, Xue YX, Liu YH (2015) Silencing of Bmi-1 gene enhances chemotherapy sensitivity in human glioblastoma cells. Med Sci Monit 21:1002–1007PubMedCentralCrossRefPubMed
Metadaten
Titel
Long noncoding RNA HOTAIR is a prognostic biomarker and inhibits chemosensitivity to doxorubicin in bladder transitional cell carcinoma
verfasst von
Chao Shang
Yan Guo
Hui Zhang
Yi-xue Xue
Publikationsdatum
01.03.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 3/2016
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-016-2964-3

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