NONO (Non-POU Domain Containing Octamer Binding)

Enforced-NONO expression restores the suppression of growth and metastasis caused by WBP11 depletion or UFL1 overexpression. Overall, our study identifies a key role of the WBP11-NONO axis in HCC progression and reveals the importance of UFMylation in cancer, highlighting potential anticancer strategies by targeting the WBP11-regulated new types of posttranslational modifications.

In conclusion, our study delineates the dual role of NONO as both a circadian regulator and a pro-tumorigenic signaling hub. By enhancing tumor-cell reception of CAF-derived signals, NONO links CRD to the formation of NONO⁺ TC niches and a malignant microenvironment in right-sided CRC, providing new mechanistic insight into the spatial heterogeneity of tumors.

Our results suggest that HDAC2 plays an oncogenic role in MB. Targeting the HDAC2/RBM47/NONO axis could be a potential therapeutic strategy for MB patients.

Finally, (R)-SKBG-1, a small molecule that modulates the RNA binding activity of NONO, hence altering its subnuclear distribution, significantly decreased cholesterol levels and SREBP target gene expression in KELLY cells. These results lend weight to manipulating NONO RNA binding as a potential therapeutic avenue for treating aggressive neuroblastoma.

At the same time, the PI3K inhibitor suppressed THP-1 cell differentiation into macrophages and attenuated the AKT phosphorylation activation by PMA and NONO knockdown during PMA-induced differentiation of THP-1 cells into macrophages. These results suggested an important role of NONO in regulating monocyte-macrophage lineage differentiation and this process was mediated, at least partially, through PI3K/AKT signaling pathway.

Mechanistically, hsa_circ_0007132 interacts with the NONO protein, impairing its ubiquitination and leading to increased stability and upregulation of NONO expression, thereby enhancing NONO-mediated nuclear export of ZEB1 mRNA and elevating ZEB1 protein expression, which ultimately contributes to LR. In summary, our findings unveil a critical mechanism through which HCC mediates tumor progression and LR via exosomal hsa_circ_0007132, while also emphasizing that targeting NONO may represent a promising therapeutic strategy to overcome LR.

Overall, these results suggest inhibition of NONO may be a promising approach for the treatment of metastatic PCa.

These findings revealed that the NONO-dependent interaction with nuclear PKM2 is key for the epigenetic modulation of TNBC metastasis, suggesting a novel intervention strategy for treating TNBC.

Our study elucidated that lncRNA GClnc1 participates in the progression of OS by regulating the NONO signal pathway. Targeting GClnc1 provides a potential target for future clinical treatment of OS.

This review provides an integrated scenario of the current understanding of the molecular mechanisms and the biological processes affected by NONO in different tumor contexts, suggesting that a better elucidation of the pleiotropic functions of NONO in physiology and tumorigenesis will make it a potential therapeutic target in cancer. In this respect, due to the complex landscape of NONO activities and interactions, we highlight caveats that must be considered during experimental planning and data interpretation of NONO studies.

In addition, IGF2BP3 disrupted the binding of RBM14 to NONO. Overall, our data elucidate the molecular mechanism by which NONO promotes DLG1 exon skipping, providing a basis for new therapeutic targets in GBC treatment.

Here we show that the topoisomerase II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-inducible antisense intergenic non-coding RNA (asincRNA) in human cancer cells...The depletion or mutation of NONO interferes with detention and prolongs DSB signalling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.