ZMYND8 suppresses MAPT213 LncRNA transcription to promote neuronal differentiation.

Zinc Finger transcription factors are crucial in modulating various cellular processes, including differentiation. Chromatin reader Zinc Finger MYND (Myeloid, Nervy, and DEAF-1) type containing 8 (ZMYND8), an All-Trans Retinoic Acid (ATRA)-responsive gene, was previously shown to play a crucial role in promoting the expression of neuronal-lineage committed genes. Here, we report that ZMYND8 promotes neuronal differentiation by positively regulating canonical MAPT protein-coding gene isoform, a key player in the axonal development of neurons.

The non-canonical nuclear functions of key players of the PI3K-AKT-MTOR pathway.

The PI3K-AKT-MTOR signal transduction pathway is one of the essential signalling cascades within the cell due to its involvement in many vital functions. The pathway initiates with the recruitment of phosphatidylinositol-3 kinases (PI3Ks) onto the plasma membrane, generating phosphatidylinositol-3,4,5-triphosphate [PtdIns(3,4,5)P ] and subsequently activating AKT. Being the central node of the PI3K network, AKT activates the mechanistic target of rapamycin kinase complex 1 (MTORC1) via Tuberous sclerosis complex 2 inhibition in the cytoplasm.

Suppression of poised oncogenes by ZMYND8 promotes chemo-sensitization.

The major challenge in chemotherapy lies in the gain of therapeutic resistance properties of cancer cells. The relatively small fraction of chemo-resistant cancer cells outgrows and are responsible for tumor relapse, with acquired invasiveness and stemness. We demonstrate that zinc-finger MYND type-8 (ZMYND8), a putative chromatin reader, suppresses stemness, drug resistance, and tumor-promoting genes, which are hallmarks of cancer.