👤 Swati

HNSCC is a highly aggressive cancer of the head and neck region, and there is an urgent need to find novel potential targets for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) have emerged as important therapeutic and diagnostic targets for multiple cancers, including HNSCC. LINC01518 promotes the proliferation of oesophageal cancer cells, but the involvement of LINC01518 in HNSCC pathophysiology is unknown. We show that LINC01518 expression is significantly upregulated in high-grade HNSCC tumor samples in comparison to normal tissue, and transforming growth factor- β (TGF-β) promotes LINC01518 expression in HNSCC cell lines. Loss-of-function studies suggest that LINC01518 promotes cell proliferation, migration, and invasion in HNSCC cells. In addition, LINC01518 depletion sensitizes HNSCC cells to cisplatin-mediated apoptosis. Mechanistically, LINC01518 acts as a competitive endogenous RNA and binds to miR-1-3p and miR-216b-5p, resulting in up-regulation of their target genes Slug and GRP78, respectively. Our findings suggest that LINC01518 is an attractive therapeutic target for HNSCC. Show less

Most antipsychotic drugs (APDs) induce hyperphagia and weight gain. However, the neural mechanisms are poorly understood, partly due to challenges replicating their metabolic effects in rodents. Here, we report a new mouse model that recapitulates overeating induced by clozapine, a widely prescribed APD. Our study shows that clozapine boosts food intake by inhibiting melanocortin 4 receptor (MC4R) expressing neurons in the paraventricular nucleus of the hypothalamus. Interestingly, neither clozapine nor risperidone, another commonly used APD, affects receptor-ligand binding or the canonical Gαs signaling of MC4R. Instead, they inhibit neuronal activity by enhancing the coupling between MC4R and Kir7.1, leading to the open state of the inwardly rectifying potassium channel. Deletion of Show less