IL-37 inhibits glycolysis of lung adenocarcinoma by inhibiting the expression of PFKFB3.

Aerobic glycolysis is one of the hallmarks of cancer. The metabolic phenotype of tumor cells is characterized by preferential dependence on glycolysis under aerobic conditions. Recent researchers have provided a piece of information on the effectiveness of targeting glycolysis. Thus, targeted glucose metabolism therapy is still a research hotspot. Interleukin 37 (IL-37) plays an important role in tumor development. Previous studies have found that IL-37 can inhibit the progression of lung adenocarcinoma in a variety of ways. For example, IL-37 can inhibit the migration and invasion of lung adenocarcinoma by inhibiting the interleukin 6(IL-6)/ Signal transducing activator of transcription 3(STAT3) pathway. IL-37 inhibits tumor growth by regulating RNA methylation at the M6A site of lung adenocarcinoma. It has been found that overexpression of IL-37 in macrophages can reverse the Warburg effect. The mechanism of IL-37 on glucose metabolism of tumor cells has not been studied. In research, glucose uptake and lactic acid production were inhibited in A549 cells with recombinant human IL-37(rhIL-37). Also, rhIL-37 inhibited the expression level of PFKFB3 in A549 cells. To verify whether the two aspects of rhIL-37's effects on A549 cells are related, we applied PFK15, a specific inhibitor of PFKFB3, to prove that rhIL-37 inhibits the glucose uptake and lactate production of A549 cells by inhibiting the expression of PFKFB3, and further inhibits the progression of lung adenocarcinoma.

Accurate detection of lung cancer-related microRNA through CRISPR/Cas9-assisted garland rolling circle amplification.

Background: MicroRNA (miRNA) is reported to be closely related to a variety of pathophysiological processes for carcinoma and considered a potential biomarker for the diagnosis of lung cancer with brain metastasis. However, developing an accurate and sensitive miRNA detection method has proven to be a challenge. The aim of the present study was to integrate the advantages of rolling circle amplification (RCA), clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nucleases 9 (Cas9), and catalytic hairpin assembly (CHA) technologies to develop an miRNA detection method. Methods: In the present study, we developed a novel approach for the sensitive and accurate detection of miRNA through integrating garland RCA and CRISPR/Cas9-assisted signal generation. In this method, target miRNA cyclized dumbbell padlock and triggered the RCA process to form long single-stranded DNA products with a repeated hairpin structure. Double-stranded DNA sequences (dsDNA) were formed with the addition of complementary sequences. With the assistance of the Cas9 enzyme for specific recognition and cleavage of formed dsDNA, RCA products were disassembled into hairpin probes. The generated hairpin probe could be unfolded by target miRNA to initiate the CHA process for signal generation. Results: Through integration of the RCA and CHA processes, the method demonstrated favorable detection performance. The correlation equation between the signal and concentration of target miRNA was determined to be Y=312.3 × lgC + 2108, with a high correlation coefficient of 0.9786. The approach also exhibited high selectivity to the mismatched miRNAs. Conclusions: Our method could be used in the screening, diagnosis, and prognosis of multiple diseases without complicated thermal cycling instrumentation.