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10.3892/etm.2017.5151

http://scihub22266oqcxt.onion/10.3892/etm.2017.5151
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C5704340!5704340!29201179
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suck abstract from ncbi


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pmid29201179      Exp+Ther+Med 2017 ; 14 (5): 4773-80
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  • Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem-like cells via induction of lncRNA HOTAIR #MMPMID29201179
  • Wang L; Dong P; Wang W; Huang M; Tian B
  • Exp Ther Med 2017[Nov]; 14 (5): 4773-80 PMID29201179show ga
  • 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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