Please use this identifier to cite or link to this item: https://doi.org/10.1186/s12864-016-3322-x
Title: Knockdown of POLA2 increases gemcitabine resistance in lung cancer cells
Authors: Koh, V
Kwan, H.Y
Tan, W.L
Mah, T.L
Yong, W.P 
Keywords: DNA directed DNA polymerase alpha
gemcitabine
small interfering RNA
antineoplastic antimetabolite
deoxycytidine
DNA directed DNA polymerase beta
gemcitabine
Article
cancer resistance
cell viability
chemosensitivity
concentration response
controlled study
drug effect
gene function
gene silencing
genetic association
genetic conservation
genetic transfection
H1299 cell line
H1650 cell line
human
human cell
lung cancer cell line
non small cell lung cancer
PC9 cell line
POLA2 gene
sequence analysis
single nucleotide polymorphism
wild type
analogs and derivatives
biology
chromosomal mapping
drug resistance
epistasis
gene expression regulation
gene silencing
genetics
lung tumor
procedures
tumor cell line
Antimetabolites, Antineoplastic
Cell Line, Tumor
Chromosome Mapping
Computational Biology
Deoxycytidine
DNA Polymerase I
Drug Resistance, Neoplasm
Epistasis, Genetic
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Lung Neoplasms
Polymorphism, Single Nucleotide
Issue Date: 2016
Publisher: BioMed Central Ltd.
Citation: Koh, V, Kwan, H.Y, Tan, W.L, Mah, T.L, Yong, W.P (2016). Knockdown of POLA2 increases gemcitabine resistance in lung cancer cells. BMC Genomics 17 : 1029. ScholarBank@NUS Repository. https://doi.org/10.1186/s12864-016-3322-x
Abstract: Background: Gemcitabine is used as a standard drug treatment for non-small cell lung cancer (NSCLC), but treatment responses vary among patients. Our previous studies demonstrated that POLA2 + 1747 GG/GA single nucleotide polymorphism (SNP) improves differential survivability and mortality in NSCLC patients. Here, we determined the association between POLA2 and gemcitabine treatment in human lung cancer cells. Results: Human PC9, H1299 and H1650 lung cancer cell lines were treated with 0.01-100 μM gemcitabine for 72 h. Although all 3 cell lines showed decreased cell viability upon gemcitabine treatment, H1299 was found to be the most sensitive to gemcitabine treatment. Next, sequencing was performed to determine if POLA2 + 1747 SNP might be involved in gemcitabine sensitivity. Data revealed that all 3 cell lines harbored the wild-type POLA2 + 1747 GG SNP, indicating that the POLA2 + 1747 SNP might not be responsible for gemcitabine sensitivity in the cell lines studied. Silencing of POLA2 gene in H1299 was then carried out by siRNA transfection, followed by gemcitabine treatment to determine the effect of POLA2 knockdown on chemosensitivity to gemcitabine. Results showed that H1299 exhibited increased resistance to gemcitabine after POLA2 knockdown, suggesting that POLA2 does not act alone and may cooperate with other interacting partners to cause gemcitabine resistance. Conclusions: Collectively, our findings showed that knockdown of POLA2 increases gemcitabine resistance in human lung cancer cells. We propose that POLA2 may play a role in gemcitabine sensitivity and can be used as a prognostic biomarker of patient outcome in NSCLC pathogenesis. © 2016 The Author(s).
Source Title: BMC Genomics
URI: https://scholarbank.nus.edu.sg/handle/10635/174242
ISSN: 14712164
DOI: 10.1186/s12864-016-3322-x
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