NR5A2 (Nuclear Receptor Subfamily 5 Group A Member 2)

This study identifies NR5A2 as a novel, actionable therapeutic target in CRC. Pharmacological modulation of NR5A2 disrupts CSC-driven stemness, potentially preventing relapse and improving treatment outcomes. These findings provide a strong rationale for the development of NR5A2-targeted therapies, either as monotherapy or in combination with chemotherapy, to optimize CRC patient care.

Furthermore, it has been determined that the high expression of NR5A2 is closely related to the resistance of MM cells to dexamethasone (Dexa). Interestingly, we found for the first time that arachidonic acid co-culture with MM cells can promote their sensitivity to Dexa and significantly reverse the resistance to Dexa caused by high expression of NR5A2. These findings provide insights into disease-causing mechanisms and new therapeutic targets for MM patients with 1q+.

Collectively, these findings reveal that LRH-1 is a novel regulator of neutrophil-driven immune responses within the tumor microenvironment. LRH-1 thus remerges as a promising therapeutic target to suppress metastasis or prevent recurrence in breast cancer.

We show that long-term estrogen deprivation (LTED) or tamoxifen treatment induces HSD3B1 expression and enzymatic activity, sustaining DHEA metabolism and ER signaling in resistant ER+ breast cancer cells...Our findings establish HSD3B1 as a critical mediator of endocrine resistance and identify LRH1 as an upstream regulator. Targeting HSD3B1 or LRH1 may offer a new therapeutic strategy to restore endocrine sensitivity in ER+ breast cancer.

Consequently, we demonstrated that phosphorylation of hLRH1S510 accelerates the viability of LUSC cells. Thus, hLRH1pS510 is attractive not only as the predictive biomarker for LUSC but also as the potential therapeutic target.

This study used ZHBTc4 ES cells, which have tetracycline-regulated Oct-4 expression, to explore the capabilities of EWS-Oct-4...Finally, comparative transcriptomic analysis revealed that ES cells expressing EWS-Oct-4 and those expressing Oct-4 had highly similar global gene expression profiles, with distinct variations in differentially expressed genes. These findings indicate that EWS-Oct-4 can effectively replace Oct-4, which has significant implications for advancements in stem cell research and regenerative medicine.

A strong additive association between CYP3A4 and CYP3A5 genotypes (informed as a CYP3A activity score [AS] variable) and lurbinectedin clearance (CL) and exposure was confirmed, for example, patients with an AS of 3, 2, or 1 showed a 2.3-, 1.6-, and 1.5-fold higher total lurbinectedin CL compared to those with an AS of 0 and 2.3-, 1.8-, and 1.6-fold higher unbound lurbinectedin CL. In conclusion, preemptive CYP3A genotyping may offer a valuable approach for personalizing treatment with lurbinectedin in cancer patients.

The specific effects of SR1848, which inhibits NR5A2, ON1231320 or BI2536, which inhibits PLK2, and blebbistatin, which inhibits MYH10, were further validated in cancer cell lines. Finally, animal studies with CCL xenografts showed the selective effect of the small molecule BI2536 on MLH1-null tumours and of blebbistatin on TP53-mutated tumours. Thus, demonstrating their potential for personalised medicine, and the robustness of genetic screening in haploid hESCs in the context of cancer therapeutics.

Therefore, this study concludes that the anti-colorectal cancer (CRC) effect of natural metabolites derived from Bifidobacterium longum is limited. Future investigations should focus on refining these natural substances and optimizing their composition ratios to extract their essence while eliminating impurities, thereby obtaining anticancer biologics with exceptional and consistent efficacy.

Co-immunoprecipitation studies revealed p53R172H and p53R245W interact with Nr5a2. These findings implicate NR5A2 as a novel mediator of mutant p53 transcriptional activity in breast cancer.

FS2 and FS4, characterized as "cold" tumors due to their decreased tumor mutation burden (TMB) and immune checkpoint proteins (ICPs), were deemed appropriate candidates for the mRNA vaccine. HOTAIR, IDO1, KIF20A, NR5A2, and RRM2 were identified as promising candidate antigens for the development of an LGG mRNA vaccine, particularly offering potential benefits to FS2 and FS4 patients.

Bioinformatics analysis of a clinical cancer database showed that NR5A2 was significantly decreased in human LUAD tissues than in normal lung tissues, and the decrease in NR5A2 gene expression shortened the overall survival and progression-free survival of patients with LUAD. The NR5A2 gene may regulate LUAD tumor stem cells through selective splicing mutations, thereby affecting the survival and prognosis of patients with lung cancer, and the NR5A2 gene may regulate CSCs through single nucleotide polymorphism.