Knockdown of long non-coding RNA PVT1 reverses multidrug resistance in colorectal cancer cells
| Autor: | Xue Qing Yao, Jian‑Hua Zhu, Heng Fan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research Small interfering RNA Cell colorectal cancer Biology Biochemistry 03 medical and health sciences 0302 clinical medicine multidrug resistance Cell Line Tumor Genetics medicine Humans PVT1 Molecular Biology Aged Messenger RNA Gene knockdown Oncogene long non-coding RNA Articles Cell cycle Middle Aged Multiple drug resistance Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Oncology Apoptosis Drug Resistance Neoplasm 030220 oncology & carcinogenesis Gene Knockdown Techniques Cancer research Molecular Medicine Female RNA Long Noncoding Fluorouracil Colorectal Neoplasms Biomarkers |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Multidrug resistance (MDR) is one of the primary causes of chemotherapy failure in colorectal cancer (CRC), and extensive biological studies into MDR are required. The non‑coding RNA plasmacytoma variant translocation 1 (PVT1) has been demonstrated to be associated with low survival rates in patients with CRC. However, whether PVT1 serves a critical function in the MDR of CRC remains to be determined. To determine the association between PVT1 expression and 5‑fluorouracil (5‑FU) resistance in CRC, the expression levels of PVT1 mRNA in 5‑FU‑resistant CRC tissues and cell lines (HCT‑8/5‑FU and HCT‑116/5‑FU) were assessed by a reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Cytotoxicity was evaluated using a Cell Counting Kit‑8 assay and apoptosis rates were assessed via flow cytometry. In the present study, PVT1 mRNA was highly expressed in 5‑FU‑resistant CRC tissues and cell lines. HCT‑8/5‑FU and HCT‑116/5‑FU cells transfected with small interfering RNA PVT1 and treated with 5‑FU exhibited higher apoptotic rates and lower survival rates. By contrast, overexpression of PVT1 in HCT‑8 and HCT‑116 cells transfected with lentiviral vector‑PVT1‑green fluorescent protein and treated with 5‑FU exhibited lower apoptosis rates and higher survival rates. RT‑qPCR and western blotting demonstrated that the overexpression of PVT1 increased the mRNA and protein expression levels of multidrug resistance‑associated protein 1, P‑glycoprotein, serine/threonine‑protein kinase mTOR and apoptosis regulator Bcl2. The present study indicates that PVT1 overexpression may promote MDR in CRC cells, and suggested that inhibition of PVT1 expression may be an effective therapeutic strategy for reversing MDR in CRC. |
| Databáze: | OpenAIRE |
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