Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

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.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 3/2016

01-03-2016 | Original Article

The long non-coding RNA HOTAIR affects the radiosensitivity of pancreatic ductal adenocarcinoma by regulating the expression of Wnt inhibitory factor 1

Authors: Yanhui Jiang, Zhihua Li, Shangyou Zheng, Huimou Chen, Xiaohui Zhao, Wenchao Gao, Zhuofei Bi, Kaiyun You, Yingxue Wang, Wenzhu Li, Liting Li, Yimin Liu, Rufu Chen

Published in: Tumor Biology | Issue 3/2016

Login to get access

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is seriously resistant to radiotherapy and the mechanism is largely unknown. HOX transcript antisense intergenic RNA (HOTAIR) is overexpressed in PDAC. However, the function of HOTAIR has never been related to the radiosensitivity of PDAC. In this present study, the expression of HOTAIR in the PDAC cell lines and tissues was measured by quantitative real-time PCR (qRT-PCR), and the association between HOTAIR expression levels and X-ray treatment in PDAC cell lines was investigated. Additionally, the influence of HOTAIR knockdown on radiosensitivity, proliferation, and apoptosis of PDAC cells after radiation was evaluated by colony formation assays, Cell Counting Kit-8 (CCK-8) assays, and flow cytometry, respectively. Furthermore, the correlation between HOTAIR and Wnt inhibitory factor 1 (WIF-1) expression in PDAC cell lines and tissues was studied to assess the role of HOTAIR and WIF-1 in the radiosensitivity of PDAC. The results confirmed that HOTAIR expression was significantly increased in the PDAC cell lines and tissues (n = 90) compared with human normal pancreatic ductal epithelial cell line (HPDE) and matched adjacent normal tissues (n = 90). Functionally, HOTAIR knockdown enhanced the radiosensitivity of PDAC cells, reduced the proliferation, and increased the apoptosis of cells after radiation. And HOTAIR silencing increased the expression of WIF-1. Furthermore, the overexpression of WIF-1 revealed that HOTAIR modulated the radiosensitivity of PDAC cells by regulating the expression of WIF-1. These data reveals that HOTAIR can affect the radiosensitivity of PDAC cells partly via regulating the expression of WIF-1, and HOTAIR-WIF-1 axis is a potential target for PDAC radiotherapy.
Appendix
Available only for authorised users
Literature
1.
2.
3.
4.
Feliu J, Borrega P, Leon A, Lopez-Gomez L, Lopez M, Castro J, et al. Phase II study of a fixed dose-rate infusion of gemcitabine associated with erlotinib in advanced pancreatic cancer. Cancer Chemother Pharmacol. 2011;67:215–21.CrossRefPubMed
5.
Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129:1311–23.CrossRefPubMedPubMedCentral
6.
7.
8.
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.CrossRefPubMed
9.
10.
11.
Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentral
12.
Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71:6320–6.CrossRefPubMed
13.
Geng YJ, Xie SL, Li Q, Ma J, Wang GY. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res. 2011;39:2119–28.CrossRefPubMed
14.
Nakagawa T, Endo H, Yokoyama M, Abe J, Tamai K, Tanaka N, et al. Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. Biochem Biophys Res Commun. 2013;436:319–24.CrossRefPubMed
15.
Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, et al. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 2013;32:1616–25.CrossRefPubMed
16.
Liu Z, Sun M, Lu K, Liu J, Zhang M, Wu W, et al. The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS One. 2013;8, e77293.CrossRefPubMedPubMedCentral
17.
Padua AC, Fonseca AS, Muys BR, de Barros ELBR, Burger MC, de Souza JE, et al. Brief report: The lincRNA Hotair is required for epithelial-to-mesenchymal transition and stemness maintenance of cancer cell lines. Stem Cells. 2013;31:2827–32.CrossRef
18.
Jing L, Yuan W, Ruofan D, Jinjin Y, Haifeng Q. HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer. Tumour Biol. 2015;36:3611–9.CrossRefPubMed
19.
Chen J, Shen Z, Zheng Y, Wang S, Mao W. Radiotherapy induced Lewis lung cancer cell apoptosis via inactivating beta-catenin mediated by upregulated HOTAIR. Int J Clin Exp Pathol. 2015;8:7878–86.PubMedPubMedCentral
20.
Ge XS, Ma HJ, Zheng XH, Ruan HL, Liao XY, Xue WQ, et al. HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway. Cancer Sci. 2013;104:1675–82.CrossRefPubMed
21.
Yan TH, Lu SW, Huang YQ, Que GB, Chen JH, Chen YP, et al. Upregulation of the long noncoding RNA HOTAIR predicts recurrence in stage Ta/T1 bladder cancer. Tumour Biol. 2014;35:10249–57.CrossRefPubMed
22.
Wang G, Li Z, Zhao Q, Zhu Y, Zhao C, Li X, et al. LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/beta-catenin signaling pathway. Oncol Rep. 2014;31:1839–45.PubMed
23.
Burris HR, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.PubMed
24.
Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AR. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol. 2002;20:3270–5.CrossRefPubMed
25.
Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea MD, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106:11667–72.CrossRefPubMedPubMedCentral
26.
Li Z, Zhao X, Zhou Y, Liu Y, Zhou Q, Ye H, et al. The long non-coding RNA HOTTIP promotes progression and gemcitabine resistance by regulating HOXA13 in pancreatic cancer. J Transl Med. 2015;13:84.CrossRefPubMedPubMedCentral
27.
28.
Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142:409–19.CrossRefPubMedPubMedCentral
29.
30.
Marchese FP, Huarte M. Long non-coding RNAs and chromatin modifiers: their place in the epigenetic code. Epigenetics. 2014;9:21–6.CrossRefPubMed
31.
Zheng CP, Han L, Hou WJ, Tang J, Wen YH, Fu R, et al. MicroRNA-9 suppresses the sensitivity of CNE2 cells to ultraviolet radiation. Mol Med Rep. 2015;12:2367–73.PubMed
32.
Huang S, Li XQ, Chen X, Che SM, Chen W, Zhang XZ. Inhibition of microRNA-21 increases radiosensitivity of esophageal cancer cells through phosphatase and tensin homolog deleted on chromosome 10 activation. Dis Esophagus. 2013;26:823–31.CrossRefPubMed
33.
Zhang X, Shi H, Lin S, Ba M, Cui S. MicroRNA-216a enhances the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy. Oncol Rep. 2015.
34.
Wang P, Zhang J, Zhang L, Zhu Z, Fan J, Chen L, et al. MicroRNA 23b regulates autophagy associated with radioresistance of pancreatic cancer cells. Gastroenterology. 2013;145:1133–43.CrossRefPubMed
35.
Stratford JK, Bentrem DJ, Anderson JM, Fan C, Volmar KA, Marron JS, et al. A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma. PLoS Med. 2010;7, e1000307.CrossRefPubMedPubMedCentral
36.
Badea L, Herlea V, Dima SO, Dumitrascu T, Popescu I. Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia. Hepatogastroenterology. 2008;55:2016–27.PubMed
37.
Collisson EA, Sadanandam A, Olson P, Gibb WJ, Truitt M, Gu S, et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med. 2011;17:500–3.CrossRefPubMedPubMedCentral
38.
39.
Zhou X, Chen J, Tang W. The molecular mechanism of HOTAIR in tumorigenesis, metastasis, and drug resistance. Acta Biochim Biophys Sin (Shanghai). 2014;46:1011–5.CrossRef
40.
Yang F, Zhang H, Mei Y, Wu M. Reciprocal regulation of HIF-1alpha and lincRNA-p21 modulates the Warburg effect. Mol Cell. 2014;53:88–100.CrossRefPubMed
41.
Zhou C, Ye L, Jiang C, Bai J, Chi Y, Zhang H. Long noncoding RNA HOTAIR, a hypoxia-inducible factor-1alpha activated driver of malignancy, enhances hypoxic cancer cell proliferation, migration, and invasion in non-small cell lung cancer. Tumour Biol. 2015.
42.
Moeller BJ, Dewhirst MW. Raising the bar: how HIF-1 helps determine tumor radiosensitivity. Cell Cycle. 2004;3:1107–10.CrossRefPubMed
43.
Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.CrossRefPubMed
44.
Wissmann C, Wild PJ, Kaiser S, Roepcke S, Stoehr R, Woenckhaus M, et al. WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer. J Pathol. 2003;201:204–12.CrossRefPubMed
45.
Gui S, Yuan G, Wang L, Zhou L, Xue Y, Yu Y, et al. Wnt3a regulates proliferation, apoptosis and function of pancreatic NIT-1 beta cells via activation of IRS2/PI3K signaling. J Cell Biochem. 2013;114:1488–97.CrossRefPubMed
46.
Cui J, Jiang W, Wang S, Wang L, Xie K. Role of Wnt/beta-catenin signaling in drug resistance of pancreatic cancer. Curr Pharm Des. 2012;18:2464–71.CrossRefPubMed
47.
Zhang Y, Morris JT, Yan W, Schofield HK, Gurney A, Simeone DM, et al. Canonical wnt signaling is required for pancreatic carcinogenesis. Cancer Res. 2013;73:4909–22.CrossRefPubMedPubMedCentral
48.
Wang L, Heidt DG, Lee CJ, Yang H, Logsdon CD, Zhang L, et al. Oncogenic function of ATDC in pancreatic cancer through Wnt pathway activation and beta-catenin stabilization. Cancer Cell. 2009;15:207–19.CrossRefPubMedPubMedCentral
49.
Lee BB, Lee EJ, Jung EH, Chun HK, Chang DK, Song SY, et al. Aberrant methylation of APC, MGMT, RASSF2A, and Wif-1 genes in plasma as a biomarker for early detection of colorectal cancer. Clin Cancer Res. 2009;15:6185–91.CrossRefPubMed
50.
Taniguchi H, Yamamoto H, Hirata T, Miyamoto N, Oki M, Nosho K, et al. Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers. Oncogene. 2005;24:7946–52.CrossRefPubMed
Metadata
Title
The long non-coding RNA HOTAIR affects the radiosensitivity of pancreatic ductal adenocarcinoma by regulating the expression of Wnt inhibitory factor 1
Authors
Yanhui Jiang
Zhihua Li
Shangyou Zheng
Huimou Chen
Xiaohui Zhao
Wenchao Gao
Zhuofei Bi
Kaiyun You
Yingxue Wang
Wenzhu Li
Liting Li
Yimin Liu
Rufu Chen
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4234-0

Other articles of this Issue 3/2016

Tumor Biology 3/2016 Go to the issue

Original Article

Skp2 regulates non-small cell lung cancer cell growth by Meg3 and miR-3163

Original Article

ROS-mediated activation of JNK/p38 contributes partially to the pro-apoptotic effect of ajoene on cells of lung adenocarcinoma

Original Article

Downregulation of miR-329 promotes cell invasion by regulating BRD4 and predicts poor prognosis in hepatocellular carcinoma

Original Article

Single nucleotide polymorphism rs11669203 in TGFBR3L is associated with the risk of neuroblastoma in a Chinese population

Original Article

XPC (A2920C), XPF (T30028C), TP53 (Arg72Pro), and GSTP1 (Ile105Val) polymorphisms in prognosis of cutaneous melanoma

Original Article

Serum chromogranin A levels for the diagnosis and follow-up of well-differentiated non-functioning neuroendocrine tumors
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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
Image Credits