Knockdown of POLA2 increases gemcitabine resistance in lung cancer cellsReport as inadecuate




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BMC Genomics

, 17:1029

First Online: 22 December 2016DOI: 10.1186-s12864-016-3322-x

Cite this article as: Koh, V., Kwan, H.Y., Tan, W.L. et al. BMC Genomics 2016 17Suppl 13: 1029. doi:10.1186-s12864-016-3322-x

Abstract

BackgroundGemcitabine 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.

ResultsHuman 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.

ConclusionsCollectively, 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.

KeywordsPOLA2 Gemcitabine Non-small cell lung cancer Drug response Single nucleotide polymorphism  Download fulltext PDF



Author: Vivien Koh - Hsueh Yin Kwan - Woei Loon Tan - Tzia Liang Mah - Wei Peng Yong

Source: https://link.springer.com/







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