METTL16 inhibits papillary thyroid cancer tumorigenicity through m6A/YTHDC2/SCD1-regulated lipid metabolism.

Papillary thyroid carcinoma (PTC) stands as the leading cancer type among endocrine malignancies, and there exists a strong correlation between thyroid cancer and obesity. However, the clinical significance and molecular mechanism of lipid metabolism in the development of PTC remain unclear. In this study, it was demonstrated that the downregulation of METTL16 enhanced lipid metabolism and promoted the malignant progression of PTC. METTL16 was expressed at lower levels in PTC tissues because of DNMT1-mediated hypermethylation of its promoter. Loss- and gain-of-function studies clarified the effects of METTL16 on PTC progression. METTL16 overexpression increased the abundance of m6A in SCD1 cells, increasing RNA decay via the m6A reader YTHDC2. The SCD1 inhibitor A939572 inhibited growth and slowed down lipid metabolism in PTC cells. These results confirm the crucial role of METTL16 in restraining PTC progression through SCD1-activated lipid metabolism in cooperation with YTHDC2. This suggests that the combination of METTL16 and anti-SCD1 blockade might constitute an effective therapy for PTC.

DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA Expression.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease is the most prevalent chronic liver disease and threats to human health. Gut dysbiosis caused by lipopolysaccharide (LPS) leakage has been strongly related to nonalcoholic fatty liver disease progression, although the underlying mechanisms remain unclear. METHODS: Previous studies have shown that low-grade LPS administration to mice on a standard, low-fat chow diet is sufficient to induce symptoms of fatty liver. This study confirmed these findings and supported LPS as a lipid metabolism regulator in the liver. RESULTS: Mechanically, LPS induced dysregulated lipid metabolism by inhibiting the expression of DNA methyltransferases 3B (DNMT3B). Genetic overexpression of DNMT3B alleviated LPS-induced lipid accumulation, whereas its knockdown increased steatosis in mice and human hepatocytes. LPS-induced lower expression of DNMT3B led to hypomethylation in promoter region of CIDEA, resulting in increased binding of SREBP-1c to its promoter and activated CIDEA expression. Hepatic interference of CIDEA reversed the effect of LPS on lipogenesis. These effects were independent of a high-fat diet or high fatty acid action. CONCLUSIONS: Overall, these findings sustain the conclusion that LPS is a lipogenic factor and could be involved in hepatic steatosis progression.

Liquid crystal-photopolymer composite films for label-free single-substrate protein quantitation and immunoassay.

Conventional liquid crystal (LC)-based biosensing at the LC-glass interface requires the assembly of an LC cell formed by two glass substrates with an LC film sandwiched in between. As most biochemical and clinical assays are performed on a single solid substrate, the feasibility of a single-substrate biodetection platform based on a thin film of LC-photopolymer composite was explored in this study. The LC mixture, consisting of nematic LC, E7 or AY40-006, doped with a small amount (≤ 5 wt%) of a photocurable prepolymer was spin-coated on a glass substrate modified with dimethyloctadecyl[3-trimethoxysilyl)propyl] ammonium chloride (DMOAP), a vertical alignment reagent, followed by irradiation with ultraviolet (UV) light. During the photopolymerization process, the accumulated and polymerized NOA65 at the LC-glass interface weakened the anchoring strength of DMOAP, resulting in a decrease in the pretilt angle of LC and allowing the LC molecules to be more easily disturbed in the presence of biomolecules, compared with vertically aligned LC in the absence of polymerized NOA65. Incorporating NOA65 in the LC film therefore provides a means for signal amplification. When an LC-photopolymer composite film consisting of AY40-006 and 4-wt% NOA65 was exposed to UV at 15 mW/cm2 for 30 s and utilized as the biosensing mesogen, the limits of detection were 1.6 × 10-12 g/ml for the direct detection of bovine serum albumin (BSA) and 2.1 × 10-8 g/ml for the immunoassay of the cancer biomarker CA125, significantly lower than those detected with AY40-006 alone or AY40-006/NOA65 mixture without UV irradiation. The results from this study offer a compelling implication on the biomedical application of LC-photopolymer composites in label-free and single-substrate biodetection.