Abstract
Abstract Background: Cellular microRNAs (miRNAs) regulate gene expression through modulation of messenger RNA transcription and are involved in epigenetic regulation, metastasis and cancer immunity. They have prognostic and therapeutic significance. The miRNAs associated with resistance in lung cancer without EGFR mutation are not yet known. We sought to determine the profile of miRNA of lung cancer cell lines without EGFR mutation treated with chemotherapy. Methods: lung cancer cell lines HTB177 were treated with PC or PCB (0.05mg/mL Cisplatin, 0.05 mg/mL pemetrexed, 6.25 mg/mL Bevacizumab) for 24, 48, 72 and 144 hours. We obtained baseline miRNA prior to therapy and after treatment to determine the changes in miRNA profile using RT PCR technique. After 144 hours, we obtained miRNA profile of the cells that survived treatment to assess change in the miRNA profile. We chose miRNA that has been reported to influence on the outcome of lung cancer: Let 7 modulates RAS, miRNA 27 is involved as tumor suppressor gene, mir212 negatively regulates antiapoptotic protein PED, miR 375 down regulates ASH1 a transcription factor. Mir21 targets anti-apoptotic genes including PDCD4 and PTEN. Results: We observed down regulation of these miRNA after 24h of treatment with PC and these miRNA then became upregulated after 48 hours, especially let 7f. In contrast, the treatment of PC with B caused upregulation of these miRNA, especially miR 27b and let 7f at 24 h and then decreased levels of upregulation at 48hours. These miRNA were not upregulated at 72h for both groups. The expression of miRNA 21 is upregulated 50 times in cells that survived treatment with PC or PCB at 144h. Conclusions: The treatment using PC and PC with B in lung cancer cell lines regulates change in the profile of miRNA at different time points. There is a difference of the miRNA profile in these 2 treatment groups. miRNA 21 is upregulated in cells resistant to therapy. miRNA could be involved in the activity of chemotherapy and development of resistance. Citation Format: Chao H. Huang, Hannah C. Motes, Siddarth Sharma, Jared Kevern, Emma Borrego-Diaz, Mukut Sharma. Determination of microRNA profile in lung cancer cell line treated with chemotherapy cisplatin (C), pemetrexed (P) or PC with bevacizumab (B) and its implication in resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1481. doi:10.1158/1538-7445.AM2017-1481
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