Abstract. Drug resistance is a primary cause of chemotherapeutic failure; however, how this resistance develops is complex. A comprehensive understanding of chemotherapeutic resistance mechanisms may aid in identifying more effective drugs and improve the survival rates of patients with cancer. Insulin-like growth factor 1 receptor (IGF1R), a member of the insulin receptor family, has been extensively assessed for biological activity, and its putative contribution to tumor cell development and progression. Furthermore, researchers have attended to drugs that target IGF1R since IGF1R functions as a membrane receptor. However, how IGF1R participates in chemotherapeutic resistance remains unclear. Therefore, the present study described the IGF1R gene and its associated signaling pathways, and offered details of IGF1R-induced tumor chemoresistance associated with promoting cell proliferation, inhibition of apoptosis, regulation of ATP-binding cassette transporter proteins and interactions with the extracellular matrix. The present study offered additional explanations for tumor chemotherapy resistance and provided a theoretical basis of IGF1R and its downstream pathways for future possible chemotherapy treatment options.
Soil organic carbon (SOC) actively participates in the global carbon (C) cycle. Despite much research, however, our understanding of the temperature sensitivity of soil organic carbon (SOC) mineralization is still very limited. To investigate the responses of SOC mineralization to temperature, we sampled surface soils (0–10 cm) from evergreen broad-leaf forest (EBF), coniferous forest (CF), sub-alpine dwarf forest (SDF), and alpine meadow (AM) along an elevational gradient in the Wuyi Mountains, China. The soil samples were incubated at 5, 15, 25, and 35°C with constant soil moisture for 360 days. The temperature sensitivity of SOC mineralization (Q10) was calculated by comparing the time needed to mineralize the same amount of C at any two adjacent incubation temperatures. Results showed that the rates of SOC mineralization and the cumulative SOC mineralized during the entire incubation significantly increased with increasing incubation temperatures across the four sites. With the increasing extent of SOC being mineralized (increasing incubation time), the Q10 values increased. Moreover, we found that both the elevational gradient and incubation temperature intervals significantly impacted Q10 values. Q10 values of the labile and recalcitrant organic C linearly increased with elevation. For the 5–15, 15–25, and 25–35°C intervals, surprisingly, the overall Q10 values for the labile C did not decrease as the recalcitrant C did. Generally, our results suggest that subtropical forest soils may release more carbon than expected in a warmer climate.
MIR17HG, located on chromosome 13, is a class of Pri-miRNAs that generates six miRNAs: miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92-1. These miRNAs are ubiquitously overexpressed in diverse tumour types and exhibit complex biological links to tumour metastasis. We demonstrated that MIR17HG-derived miR-18a and miR-19a coordinately mediate gastric cancer cell metastasis by directly inhibiting SMAD2 expression and upregulating Wnt/β-catenin signalling. Based on previous studies, we hypothesised that an investigation of MIR17HG inhibition would be beneficial to clinical gastric cancer treatment, and systematically coupled bioinformatics analyses brought interferon regulatory factor-1 (IRF-1) to our attention. We then established stable clones in gastric cancer cells containing a doxycycline-inducible IRF-1 expression system and found that the expression of IRF-1 downregulates the embedded miRNAs of MIR17HG in gastric cancer cells and inhibits gastric cancer cell metastasis by attenuating Wnt/β-catenin signalling. Further rescue assays confirmed the crucial roles of miR-18a and miR-19a in the IRF-1-mediated inhibition of Wnt/β-catenin signalling. We also demonstrated that IRF-1 binds to the transcriptional site in the MIR17HG promoter and inhibits MIR17HG expression. Moreover, IFN-γ induced the IRF-1-mediated downregulation of MIR17HG in gastric cancer cells. Our hypothesis was supported by the results of immunohistochemistry analyses of clinical gastric cancer samples, and we also demonstrated the role of IRF-1 in inhibiting MIR17HG expression and tumour metastasis in vivo. We conclude that IRF-1 inhibits gastric cancer metastasis by downregulating MIR17HG-miR-18a/miR-19a axis expression and attenuating Wnt/β-catenin signalling.
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