IGF2BP3 enhances lipid metabolism in cervical cancer by upregulating the expression of SCD.

Cervical cancer (CC) is the most common gynecologic malignancy, which seriously threatens the health of women. Lipid metabolism is necessary for tumor proliferation and metastasis. However, the molecular mechanism of the relationship between CC and lipid metabolism remains poorly defined. We revealed the expression of IGF2BP3 in CC exceeded adjacent tissues, and was positively associated with tumor stage using human CC tissue microarrays. The Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay, transwell assays, wound-healing assays, and flow cytometry assessed the role of IGF2BP3 in proliferation and metastasis of CC cells. Besides, exploring the molecular mechanism participating in IGF2BP3-driven lipid metabolism used RNA-seq, which determined SCD as the target of IGF2BP3. Further, lipid droplets, cellular triglyceride (TG) contents, and fatty acids were accessed to discover that IGF2BP3 can enhance lipid metabolism in CC. Moreover, RIP assay and methylated RNA immunoprecipitation experiments seeked the aimed-gene-binding specificity. Lastly, the IGF2BP3 knockdown restrained CC growth and lipid metabolism, after which SCD overexpression rescued the influence in vitro and in vivo using nude mouse tumor-bearing model. Mechanistically, IGF2BP3 regulated SCD mRNA m6A modifications via IGF2BP3-METTL14 complex, thereby enhanced CC proliferation, metastasis, and lipid metabolism. Our study highlights IGF2BP3 plays a crucial role in CC progression and represents a therapeutic latent strategy. It is a potential tactic that blocks the metabolic pathway relevant to IGF2BP3 with the purpose of treating CC.

Mechanism research of srtA gene on the oxidation tolerance of Streptococcus mutans / 口腔疾病防治

Objective@#To investigate the effects of srtA on the oxidation tolerance of the Streptococcus mutans UA159 strain and to explore the potential mechanism.@*Methods@#The oxidation tolerance in the planktonic state and biofilm state were compared among UA159, the srtA-deleted strain and the complementary strain through oxidative tolerance experiments. The RNA-sequencing data from both the exponential and stationary phases of UA159 and the srtA-deleted strain were obtained by using the Illumina HiSeq 4 000 sequencing platform to determine the impact of srtA knockout on S. mutans genomic transcription. We compared the differences in the transcriptional expression of oxidative tolerance-related genes between the UA159 strain and the srtA gene deletion strain and further explored the intrinsic relationship between the changes in oxidative tolerance and the genetic transcriptome. qPCR was used to verify the changes in the expression level of oxidation tolerance-related genes.@*Results @#The oxidation tolerance of the srtA-deleted strain decreased significantly in both the planktonic state and the biofilm state compared to that of UA159 (P < 0.05). A total of 33 oxidation tolerance-related genes were differentially expressed according to transcriptome sequencing. There was no significant change in the expression of peroxide synthesis- and metabolic-related enzyme genes, but in the stationary phase samples, the two-component signal transcription systems lrgA, lrgB, and lytT were significantly downregulated (2.2- to 2.4-fold) in the srtA-deleted strain. qPCR further confirmed that in both the exponential and stationary phases, lrgB and lytT expression in the planktonic state was reduced 11.01-53.51-fold, while the expression of the other two-component system-encoding gene vicK was reduced by 6.57-10.88-fold (P < 0.001).@*Conclusion@#SrtA gene deletion did not change the expression level of peroxide synthesis-related and metabolic enzyme-encoding genes but downregulated the expression of the associated transcription regulation factors to reduce the oxidation tolerance of S. mutans.