Under poor conditions (such as DNA damage or hypoxic oxygen), tumor suppressor genes such as P53 can trigger apoptosis 44 . P53 is one of the most common mutation genes in human tumors. resistance and its relationship with microRNAs. found EGFR self-resistance mutation, T790M second mutation and the activation of the PI3K/AKT signal pathways 4. In 2007 Lim found that gene of phosphate and tension homology deleted on chromosome ten (PTEN) mutations and Axl overexpression 5. In 2005 Pao found that kirsten rat sarcoma viral oncogene (KRAS), v-raf murine asrcoma viral oncogene homolog B1 (BRAF) and human epidermal growth factor receptor-2 (HER-2) mutations 6. In 2007 Engelman found that mesenchymal-epithelial transition (MET) factor proto oncogene amplification and overexpression of protein 7. There are also some mechanisms concerned with signal pathways. For example, in 2014 Wu found that epithelial-mesenchymal transition (EMT) cell growth related to the deletion of signal pathways 8. Most of the above-mentioned mechanisms of lung cancer resistance are related to gene mutation, deletion and amplification. In addition to the above-mentioned lung cancer resistance mechanisms, there are other lung cancer resistance mechanisms involving pharmacokinetics and multidrug resistance genes, such as the following aspects. i) In 2016 Wei found that membrane transporter-mediated drug efflux pump mechanism, as the most common mechanism, which can reduce intracellular drug accumulation. This mechanism involves overexpressed membrane protein with efflux pump, such as ABC family member P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP) and so on 9. ii) Intracellular abnormal enzyme system can be combined Rabbit polyclonal to KATNB1 with a variety of chemotherapeutic drugs, which reduces drug activity, or enhances the DNA repair ability of tumor cells, and prevent the damage of chemotherapeutic drugs to the tumor cells 10. These intracellular abnormal enzymes are overexpressed topoisomerase, glutamyl transpeptidase, found that anti-apoptotic effect of cells is enhanced, such as over-expression of anti-apoptotic genes bcl-2 and c-myc, which makes tumor cells less susceptible to apoptosis 11. The epidermal growth factor receptor (EGFR) is a member of a family of four BMS-962212 closely related receptors: EGFR (or erbB1), HER2/neu (erbB2), HER3 (erbB3) and HER4 (erbB4) 12. Approximately 50% of Asian patients with NSCLC have EGFR mutations 13. Patients with sensitizing mutations of EGFR, compared to conventional chemotherapy, these targeted therapy, such as epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved huge success and became one of the standard treatment-regimes for NSCLC. However, patients ultimately develop resistance to these drugs, even though EGFR-TKIs have been established as the standard therapy for EGFR-sensitizing mutant advanced NSCLC clinically 14, 15. According to the current mechanisms of lung cancer resistance, researchers have classified them into two categories: primary and acquired resistance. The primary resistance is defined as the failure to respond to the treatments at the first time after receiving EGFR-TKIs and presents no obvious improvement in symptoms, disease control or overall survival. Approximately 85% of all primary BMS-962212 lung cancers are NSCLC. While some patients with activating EGFR mutations who are initially responsive to EGFR TKIs very well at firstly, eventually would be developed acquired resistance after a complete or partial response or 6 months of stable disease after treatment with a targeted therapy 16. Strategies to overcome these intrinsic and acquired resistance mechanisms are complex. Thus studies on the lung cancer drug resistance are extremely important in order to define the best treatment strategy. MicroRNAs (miRNAs, miRs) are a class of small endogenous single strand non-coded RNA, about 19-25 nt, found in eukaryotes, and have the function of regulating after gene transcription 15. MicroRNAs’ regulation mechanism is that the longer miRNAs primary transcript produces mature miRNAs through a series of nuclease shear processing. Then these mature miRNAs are assembled into the RNA-induced silencing complex (RISC). Then mature miRNAs recognize and combine the target genes or the target mRNAs’ 3′ terminal non translation region (UTR) by complementary pairing of bases. The RISC will conduct the process of mRNAs’ degradation or inhibition of their translations. MiRNAs and target mRNAs combined incompletely can inhibit the expression of mRNAs at the level of protein translation. While when they may complement each BMS-962212 other completely (or almost completely complementary), which can degrade the target mRNAs degradation and change the expression level of the target protein, then achieve the regulatory effect 17. In 2016 Ren found that miRNAs can regulate a variety.