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Y. Li
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-095 - Basic Transcription Factor 3 Is Involved in Lung Cancer Growth and Progression (ID 7395)
09:30 - 09:30 | Author(s): Y. Li
- Abstract
Background:
Basic transcription factor 3 (BTF3) which is a general RNA polymerase II transcription factor plays a crucial role in the regulation of various biological processes. Evidence has demonstrated that BTF3 is aberrantly expressed and involved in the development and progression of gastric cancer and colorectal cancer. However, the role of BTF3 in lung cancer is not clear. The present study is to investigate the expression of BTF3 in non-small cell lung caner (NSCLC), its role in tumor growth as well as the underlying mechanisms.
Method:
BTF3 shRNA lentiviral vector was constructed and transfected in human NSCLC cells NCI-H1299 and A549. The cell proliferation, viability and apoptosis were evaluated by Celigo, MTT and AnnexinV-APC assays. The immunohistochemical stainings of BTF3 were performed on ten NSCLC tumors and matched adjacent lung tissues. Xenograft tumor model was established to evaluate the role of BTF3 in tumor formation in vivo. To further explore the underlying mechanism, a gene array was performed in BTF3 knockdowned A549 cells and pathway/network analyses was performed with Ingenuity Pathway Analysis (IPA).
Result:
Knockdown of BTF3 inhibited the proliferation and viability and increased apoptosis significantly in NSCLC cells. The BTF3 expression was much higher in NSCLC tumors compared to the adjacent lung tissues. A549 with BTF3 shRNA lentiviral transfection could not form subcutaneous tumors in immune-deficient mice in vivo. After BTF3 was inhibited in A549 cells, it was observed 489 upregulated and 148 downregulated genes (FC>1.5). IPA core analysis of these proteins revealed that acute phase response pathway was significantly enriched among other canonical pathways, and played a role in cell death, cell movement of myeloid cells and organismal death. We further utilized IPA upstream regulator analysis and found two transcriptional regulators XBP1 and NUPR1 that are predicted to be the key regulators of proteins changed in the BTF3 inhibited A549 cells. Western blot analysis verified that HK2, DUSP5 and KLF4 were significantly downregulated in BTF3 inhibited A549 cells.
Conclusion:
These results suggest, for the first time, that BTF3 is over-expressed in lung cancer and favors tumor growth, suggesting that BTF3 might play a role in the progression of lung cancer. The investigation of BTF3 in NSCLC survival and prognosis and further regulatory mechanisms are ongoing.
