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Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR

  • Authors:
    • Li Wang
    • Ping Dong
    • Weiguo Wang
    • Mingquan Huang
    • Bole Tian
  • View Affiliations / Copyright

    Affiliations: Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610064, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4773-4780
    |
    Published online on: September 20, 2017
       https://doi.org/10.3892/etm.2017.5151
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Abstract

Gemcitabine is the first‑line chemotherapeutic agent for advanced adenocarcinoma of the pancreas, despite the high risk of chemoresistance as a major disadvantage. In the past few years, significant advances have been made in the field of pancreatic cancer stem‑like cells (CSCs) and their critical roles in drug resistance, invasion and metastasis, which are tightly regulated by long non‑coding RNAs (lncRNAs). The present study demonstrated that HOX antisense intergenic RNA (HOTAIR) is not different between the pancreatic cancer cell line PANC‑1 and its enriched CSC sub‑population. However, after gemcitabine treatment, the expression levels of HOTAIR in CSCs were induced, but not in PANC‑1 cells. HOTAIR induced by gemcitabine failed to cause chemoresistance, but promoted the clonogenicity, proliferation and migration of the cells. By introducing HOTAIR using lentivirus, chemoresistance was induced and the self‑renewal capacity, proliferation and migration were significantly promoted. By contrast, HOTAIR knockdown in PANC‑1 CSCs treated with or without gemcitabine decreased the cell proliferation, altered the cell cycle progression and induced apoptosis, demonstrating its critical roles in regulating the malignant character of PANC‑1 CSCs. In conclusion, the present study demonstrated that HOTAIR may be induced by gemcitabine and acts as a tumor promoter by inhibiting the chemosensitivity, and promoting the self‑renewal capacity, proliferation and migration of PANC‑1 CSCs, which supports its potential application as a novel therapeutic approach for pancreatic cancer.
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1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Li D, Xie K, Wolff R and Abbruzzese JL: Pancreatic cancer. Lancet. 363:1049–1057. 2004. View Article : Google Scholar : PubMed/NCBI

3 

O'Reilly EM and Abou-Alfa GK: Cytotoxic therapy for advanced pancreatic adenocarcinoma. Semin Oncol. 34:347–353. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Wang Z, Li Y, Ahmad A, Banerjee S, Azmi AS, Kong D and Sarkar FH: Pancreatic cancer: Understanding and overcoming chemoresistance. Nat Rev Gastroenterol Hepatol. 8:27–33. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Bergman AM, Pinedo HM and Peters GJ: Determinants of resistance to 2′,2′-difluorodeoxycytidine (gemcitabine). Drug Resist Updat. 5:19–33. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Andersson R, Aho U, Nilsson BI, Peters GJ, Pastor-Anglada M, Rasch W and Sandvold ML: Gemcitabine chemoresistance in pancreatic cancer: Molecular mechanisms and potential solutions. Scand J Gastroenterol. 44:782–786. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Polyak K and Hahn WC: Roots and stems: Stem cells in cancer. Nat Med. 12:296–300. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Kakarala M and Wicha MS: Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol. 26:2813–2820. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J and Dirks PB: Identification of a cancer stem cell in human brain tumors. Cancer Res. 63:5821–5828. 2003.PubMed/NCBI

10 

Abdullah LN and Chow EK: Mechanisms of chemoresistance in cancer stem cells. Clin Transl Med. 2:32013. View Article : Google Scholar : PubMed/NCBI

11 

Ucar D, Cogle CR, Zucali JR, Ostmark B, Scott EW, Zori R, Gray BA and Moreb JS: Aldehyde dehydrogenase activity as a functional marker for lung cancer. Chem Biol Interact. 178:48–55. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Jimeno A, Feldmann G, Suárez-Gauthier A, Rasheed Z, Solomon A, Zou GM, Rubio-Viqueira B, García-García E, López-Ríos F, Matsui W, et al: A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development. Mol Cancer Ther. 8:310–314. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Hellsten R, Johansson M, Dahlman A, Sterner O and Bjartell A: Galiellalactone inhibits stem cell-like ALDH-positive prostate cancer cells. PLoS One. 6:e221182011. View Article : Google Scholar : PubMed/NCBI

14 

Ma S, Chan KW, Lee TK, Tang KH, Wo JY, Zheng BJ and Guan XY: Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol Cancer Res. 6:1146–1153. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Clay MR, Tabor M, Owen JH, Carey TE, Bradford CR, Wolf GT, Wicha MS and Prince ME: Single-marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase. Head Neck. 32:1195–1201. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Yin T, Wei H, Gou S, Shi P, Yang Z, Zhao G and Wang C: Cancer stem-like cells enriched in Panc-1 spheres possess increased migration ability and resistance to gemcitabine. Int J Mol Sci. 12:1595–1604. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Yang G, Lu X and Yuan L: LncRNA: A link between RNA and cancer. Biochim Biophys Acta. 1839:1097–1109. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Jiao F, Hu H, Han T, Yuan C and Wang L, Jin Z, Guo Z and Wang L: Long noncoding RNA MALAT-1 enhances stem cell-like phenotypes in pancreatic cancer cells. Int J Mol Sci. 16:6677–6693. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Zhuang Y, Wang X, Nguyen HT, Zhuo Y, Cui X, Fewell C, Flemington EK and Shan B: Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen. J Hematol Oncol. 6:352013. View Article : Google Scholar : PubMed/NCBI

20 

Zhang A, Zhao JC, Kim J, Fong KW, Yang YA, Chakravarti D, Mo YY and Yu J: LncRNA HOTAIR enhances the androgen-receptor-mediated transcriptional program and drives castration-resistant prostate cancer. Cell Rep. 13:209–221. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S and Safe S: HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 32:1616–1625. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Tahira AC, Kubrusly MS, Faria MF, Dazzani B, Fonseca RS, Maracaja-Coutinho V, Verjovski-Almeida S, Machado MC and Reis EM: Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer. Mol Cancer. 10:1412011. View Article : Google Scholar : PubMed/NCBI

23 

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

24 

Lee CJ, Dosch J and Simeone DM: Pancreatic cancer stem cells. J Clin Oncol. 26:2806–2812. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Hermann PC, Mueller MT and Heeschen C: Pancreatic cancer stem cells-insights and perspectives. Expert Opin Biol Ther. 9:1271–1278. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Habib M and Saif MW: Pancreatic cancer stem cells: Their role in pancreatic cancer patient outcomes and what is future? JOP. 14:401–404. 2013.PubMed/NCBI

27 

Cioffi M, Trabulo SM, Sanchez-Ripoll Y, Miranda-Lorenzo I, Lonarod E, Dorado J, Vieira Reis C, Ramirez JC, Hidalgo M, Aicher A, et al: The miR-17-92 cluster counteracts quiescence and chemoresistance in a distinct subpopulation of pancreatic cancer stem cell. Gut. 64:1936–1948. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Goodell MA, Brose K, Paradis G, Conner AS and Mulligan RC: Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 183:1797–1806. 1996. View Article : Google Scholar : PubMed/NCBI

29 

Hilton J: Role of aldehyde dehydrogenase in cyclophosphamide-resistant L1210 leukemia. Cancer Res. 44:5156–5160. 1984.PubMed/NCBI

30 

Kim R, Emi M and Tanabe K: Role of mitochondria as the gardens of cell death. Cancer Chemother Pharmacol. 57:545–553. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Li L, Gu M, You B, Shi S, Shan Y, Bao L and You Y: Long non-coding RNA ROR promotes proliferation, migration and chemoresistance of nasopharyngeal carcinoma. Cancer Sci. 107:1215–1222. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Liu J, Wan L, Lu K, Sun M, Pan X, Zhang P, Lu B, Liu G and Wang Z: The long noncoding RNA MEG3 contributes to cisplatin resistance of human lung adenocarcinoma. PLoS One. 10:e01145862015. View Article : Google Scholar : PubMed/NCBI

33 

Yang Y, Li H, Hou S, Hu B, Liu J and Wang J: The noncoding RNA expression profile and the effect of lncRNAAK126698 on cisplatin resistance in non-small-cell lung cancer cell. PLoS One. 8:e653092013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang L, Dong P, Wang W, Huang M and Tian B: Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR. Exp Ther Med 14: 4773-4780, 2017.
APA
Wang, L., Dong, P., Wang, W., Huang, M., & Tian, B. (2017). Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR. Experimental and Therapeutic Medicine, 14, 4773-4780. https://doi.org/10.3892/etm.2017.5151
MLA
Wang, L., Dong, P., Wang, W., Huang, M., Tian, B."Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR". Experimental and Therapeutic Medicine 14.5 (2017): 4773-4780.
Chicago
Wang, L., Dong, P., Wang, W., Huang, M., Tian, B."Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR". Experimental and Therapeutic Medicine 14, no. 5 (2017): 4773-4780. https://doi.org/10.3892/etm.2017.5151
Copy and paste a formatted citation
x
Spandidos Publications style
Wang L, Dong P, Wang W, Huang M and Tian B: Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR. Exp Ther Med 14: 4773-4780, 2017.
APA
Wang, L., Dong, P., Wang, W., Huang, M., & Tian, B. (2017). Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR. Experimental and Therapeutic Medicine, 14, 4773-4780. https://doi.org/10.3892/etm.2017.5151
MLA
Wang, L., Dong, P., Wang, W., Huang, M., Tian, B."Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR". Experimental and Therapeutic Medicine 14.5 (2017): 4773-4780.
Chicago
Wang, L., Dong, P., Wang, W., Huang, M., Tian, B."Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem‑like cells via induction of lncRNA HOTAIR". Experimental and Therapeutic Medicine 14, no. 5 (2017): 4773-4780. https://doi.org/10.3892/etm.2017.5151
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