Inhibition of PSF activity overcomes resistance to treatment in cancers harboring mutant p53.

Mutations in the TP53 tumor suppressor genes are prevalent in aggressive cancers. Pharmacological reactivation of dysfunctional p53 due to mutations is a promising strategy for treating such cancers. Recently, a multifunctional proline- and glutamine-rich protein, PTB-associated splicing factor (PSF), was identified as a key driver of aggressive cancers.

ERRα and ERRγ coordinate expression of genes associated with Alzheimer's disease, inhibiting to suppress tau phosphorylation.

Alzheimer's disease (AD) is a prevalent neurodegenerative disease characterized by cognitive decline and learning/memory impairment associated with neuronal cell loss. Estrogen-related receptor α (ERRα) and ERRγ, which are highly expressed in the brain, have emerged as potential AD regulators, with unelucidated underlying mechanisms. Here, we identified genome-wide binding sites for ERRα and ERRγ in human neuronal cells.

Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancer.

Although hormone therapy is effective for the treatment of prostate cancer (Pca), many patients develop a lethal type of Pca called castration-resistant prostate cancer (CRPC). Dysregulation of DNA damage response (DDR)-related genes leads to Pca progression. Here, we explored DDR-related signals upregulated in CRPC tissues.

Expression and function of estrogen receptors and estrogen-related receptors in the brain and their association with Alzheimer's disease.

While estrogens are well known for their pivotal role in the female reproductive system, they also play a crucial function in regulating physiological processes associated with learning and memory in the brain. Moreover, they have neuroprotective effects in the pathogenesis of Alzheimer's disease (AD). Importantly, AD has a higher incidence in older and postmenopausal women than in men, and estrogen treatment might reduce the risk of AD in these women.

Identification of small-molecule inhibitors against the interaction of RNA-binding protein PSF and its target RNA for cancer treatment.

Diverse cellular activities are modulated through a variety of RNAs, including long noncoding RNAs (lncRNAs), by binding to certain proteins. The inhibition of oncogenic proteins or RNAs is expected to suppress cancer cell proliferation. We have previously demonstrated that PSF interaction with its target RNAs, such as androgen-induced lncRNA , is critical for hormone therapy resistance in prostate and breast cancers.

Stress granules sequester Alzheimer's disease-associated gene transcripts and regulate disease-related neuronal proteostasis.

Environmental and physiological stresses can accelerate Alzheimer's disease (AD) pathogenesis. Under stress, a cytoplasmic membraneless structure termed a stress granule (SG) is formed and is associated with various neurodegenerative disorders, including AD. SGs contain translationally arrested mRNAs, suggesting that impaired RNA metabolism in neurons causes AD progression; however, the underlying mechanism remains unclear.

Ribonuclease H2 Subunit A Preserves Genomic Integrity and Promotes Prostate Cancer Progression.

Unlabelled: Homeostasis of genomic integrity should be regulated to promote proliferation and inhibit DNA damage-induced cell death in cancer. Ribonuclease H2 (RNase H2) maintains genome stability by controlling DNA:RNA hybrid and R-loop levels. Here, we identified that RNase H2 subunit A (RNASEH2A), a component of RNase H2, is highly expressed in castration-resistant prostate cancer (CRPC) tissues compared with localized prostate cancer.

Transcriptional and Post-Transcriptional Regulations of Amyloid-β Precursor Protein APP mRNA.

Alzheimer's disease (AD) is an age-associated neurodegenerative disorder characterized by progressive impairment of memory, thinking, behavior, and dementia. Based on ample evidence showing neurotoxicity of amyloid-β (Aβ) aggregates in AD, proteolytically derived from amyloid precursor protein (APP), it has been assumed that misfolding of Aβ plays a crucial role in the AD pathogenesis. Additionally, extra copies of the gene caused by chromosomal duplication in patients with Down syndrome can promote AD pathogenesis, indicating the pathological involvement of the gene dose in AD.

Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer.

Interactive networks of transcription factors (TFs) have critical roles in epigenetic and gene regulation for cancer progression. It is required to clarify underlying mechanisms for transcriptional activation through concerted efforts of TFs. Here, we show the essential role of disease phase-specific TF collaboration changes in advanced prostate cancer (PC).

Targeting Epigenetic and Posttranscriptional Gene Regulation by PSF Impairs Hormone Therapy-Refractory Cancer Growth.

RNA-binding protein PSF functions as an epigenetic modifier by interacting with long noncoding RNAs and the corepressor complex. PSF also promotes RNA splicing events to enhance oncogenic signals. In this study, we conducted an chemical array screen and identified multiple small molecules that interact with PSF.

Identification of long non-coding RNAs in advanced prostate cancer associated with androgen receptor splicing factors.

The molecular and cellular mechanisms of development of castration-resistant prostate cancer (CRPC) remain elusive. Here, we analyzed the comprehensive and unbiased expression profiles of both protein-coding and long non-coding RNAs (lncRNAs) using RNA-sequencing to reveal the clinically relevant molecular signatures in CRPC tissues. For protein-coding genes upregulated in CRPC, we found that mitochondria-associated pathway, androgen receptor (AR), and spliceosome associated genes were enriched.

Polyethylene glycol derivative 9bw suppresses growth of neuroblastoma cells by inhibiting oxidative phosphorylation.

Neuroblastoma (NB) is a childhood malignancy originating from the sympathetic nervous system, and accounts for approximately 15% of all pediatric cancer-related deaths. As the 5-y survival rate of patients with high-risk NB is <50%, novel therapeutic strategies for NB patients are urgently required. Nonaethylene glycol mono('4-iodo-4-biphenyl)ester (9bw) is a polyethylene glycol derivative, synthesized by modifying a compound originally extracted from filamentous bacteria.

TRIM44 promotes cell proliferation and migration by inhibiting FRK in renal cell carcinoma.

TRIM44 has oncogenic roles in various cancers. However, TRIM44 expression and its function in renal cell carcinoma (RCC) are still unknown. Here in this study, we investigated the clinical significance of TRIM44 and its biological function in RCC.

RNA-binding protein NONO promotes breast cancer proliferation by post-transcriptional regulation of SKP2 and E2F8.

The majority of breast cancers are primarily hormone-sensitive and can be managed by endocrine therapy, although therapy-resistant or hormone-refractory cancers need alternative treatments. Recently, increasing attention is being paid to RNA-binding proteins (RBP) in cancer pathophysiology. The precise role of RBP in breast cancer, however, remains to be clarified.

Amyloid precursor protein, an androgen-regulated gene, is targeted by RNA-binding protein PSF/SFPQ in neuronal cells.

Amyloid precursor protein (APP) is a representative gene related to Alzheimer's disease (AD). Androgens function by binding to the androgen receptor (AR). Both androgen and RNA-binding protein PSF play a role in the pathology of AD.

Identification of new octamer transcription factor 1-target genes upregulated in castration-resistant prostate cancer.

Octamer transcription factor 1 (OCT1) is an androgen receptor (AR)-interacting partner and regulates the expression of target genes in prostate cancer cells. However, the function of OCT1 in castration-resistant prostate cancer (CRPC) is not fully understood. In the present study, we used 22Rv1 cells as AR-positive CRPC model cells to analyze the role of OCT1 in CRPC.

Ginsenoside Rb1 inhibits vascular calcification as a selective androgen receptor modulator.

Ginsenoside Rb1 (Rb1), a major component of ginseng, has a steroidal chemical structure, implying that it exerts sex hormone-like actions. Recent studies have been suggested cardioprotective actions of Rb1. However, the actions of Rb1 in vascular calcification, one of the significant pathological features associated with aging and atherosclerosis, have not been examined.