The natural genetic variation in pre-miR-146a affects the amount of mature miR-146a, contributes to the genetic predisposition to CaP.

Background: As a rate-limiting enzyme of glycolysis, pyruvate kinase muscle isozyme M2 (PKM2) participates in tumor metabolism and growth. The regulatory network of PKM2 in cancer is complex and has not been fully studied in bladder cancer. The 5-methylcytidine (m5C) modification in PKM2 mRNA might participate in the pathogenesis of bladder cancer and need to be further clarified. This study aimed to investigate the biological function and regulatory mechanism of PKM2 in bladder cancer. Methods:The expression of PKM2 and Aly/REF export factor (ALYREF) was measured by Western blotting, qRT-PCR, and immunohistochemistry. The bioprocesses of bladder cancer cells were demonstrated by a series of experiments in vitro and in vivo. RNA immunoprecipitation, RNA-sequencing, and dualluciferase reporter assays were conducted to explore the potential regulatory mechanisms of PKM2 in bladder cancer. Results:In bladder cancer, we first demonstrated that ALYREF stabilized PKM2 mRNA and bound to its m5C sites in 3′-untranslated regions. Overexpression of ALYREF promoted bladder cancer cell proliferation by PKM2-mediated glycolysis. Furthermore, high expression of PKM2 and ALYREF predicted poor survival in bladder cancer patients. Finally, we found that hypoxia-inducible factor-1alpha (HIF-1α) indirectly up-regulated the expression of PKM2 by activating ALYREF in addition to activating its transcription directly. Conclusions:The m5C modification in PKM2 mRNA in the HIF-1α/ALYREF/PKM2 axis may promote the glucose metabolism of bladder cancer, providing a new promising therapeutic target for bladder cancer.

Graphene oxide (GO) exhibits excellent adsorption ability to remove organic dyes from liquid; therefore, fabricating GO-based adsorbents has attracted increasing interest from researchers. However, it is still challenging to prepare the GO-based adsorbents with high structure stability while simultaneously maintaining its high adsorption ability. In this work, a novel one-step fabrication method combining exfoliating and micro-cross-linking simultaneously was proposed to prepare the GO composite aerogel globules, in which GO was exfoliated by carboxymethyl cellulose (CMC) in the globule center, whereas the globule was micro-cross-linked by chitosan (CS) on the surface. The results showed that there were strong interactions between components, and the composite aerogel globule exhibited multiscale porous structures on the globule surface and the highly porous structure in the globule center. The composite aerogel exhibited high structure stability in liquid. The adsorption measurements toward methylene blue (MB) showed that the CS-GO/CMC composite aerogel had extremely high adsorption capacity, and the maximum adsorption capacity was 3190 mg/g for the CS-GO/CMC-1/1 composite aerogel, which was the highest adsorption capacity reported in the literature. The adsorption kinetics, adsorption isotherms, and the adsorption thermodynamics were comparatively investigated. The results showed that the adsorption of MB obeyed a pseudo-second-order model and Langmuir adsorption model, and the adsorption was a spontaneous process. Furthermore, the composite aerogel also showed excellent removal ability for Cr­(VI), and the adsorption capacity was 127.4 mg/g. The extremely high adsorption abilities toward MB and Cr­(VI) and high structural stability in liquid endow the CS-GO/CMC composite aerogel with potential applications in wastewater treatment.