LINC01320 facilitates cell proliferation and migration of ovarian cancer via regulating PURB/DDB2/NEDD4L/TGF-ß axis.

Ovarian cancer (OC) is one of the most prevalent and lethal malignancies affecting the female reproductive system, due to its tendency for metastasis and recurrence. This study identified the overexpression of LINC01320 (or long intergenic nonprotein coding RNA 1320) in tissues of ovarian cancer through the analysis of patient samples and online datasets. In vitro and in vivo experiments demonstrate that silencing of LINC01320 expression led to inhibition of proliferation and metastasis of OC cells. RNA pull-down followed by liquid chromatography tandem mass spectrometry (RNA pull-down-LC-MS/MS) revealed that LINC01320 interacted with purine-rich element binding protein B (PURB), a transcriptional repressor. Furthermore, the RNA-seq analysis identified damage-specific DNA binding protein 2 (DDB2) as a major common target of LINC01320 and PURB. Mechanistically, LINC01320 could recruit PURB to the promoter region of DDB2 to repress DDB2 transcription; thus, promoting the expression of NEDD4L and impeding the TGF-ß/SMAD signaling pathway, and ultimately facilitating the progression of OC. Finally, rescue experiments confirmed the involvement of the DDB2/NEDD4L/TGF-ß axis in LINC01320-mediated OC progression. In conclusion, this study unveils for the first time the pivotal function of the LINC01320/PURB/DDB2/NEDD4L/TGF-ß axis and explores its prospective clinical implications in OC.

E3 ligase FBXO22 is not significant for spermatogenesis and male fertility in mice.

BACKGROUND: F-box-only protein 22 (FBXO22), an important substrate receptor of the SKP1-Cullin-F-box (SCF) ubiquitin ligases, has been reported to be involved in many biological processes, including tumorigenesis, neurological disorders, cellular senescence, and DNA damage. However, the specific role of FBXO22 during spermatogenesis is poorly understood. METHODS: We produced Fbxo22 conditional knockout (cKO) and global knockout (KO) mice and assessed their sperm masurements using a computer-assisted sperm analysis (CASA) system. Additionally, we conducted histologic staining and immunostaining to examine the impact of Fbxo22 loss on spermatogenesis. RESULTS: Our results revealed that there were no notable differences in semen quality, fertility test results, or histologic findings in Fbxo22-KO and Fbxo22-cKO mice compared to the control group. CONCLUSIONS: Our study demonstrated that Fbxo22 is not significant for spermatogenesis or male fertility in mice. These findings will help researchers avoid redundant efforts and serve as a foundational resource for genetic studies on human fertility.

RNF187 governs the maintenance of mouse GC-2 cell development by facilitating histone H3 ubiquitination at K57/80.

RING finger 187 (RNF187), a ubiquitin-ligating (E3) enzyme, plays a crucial role in the proliferation of cancer cells. However, it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells. To investigate the potential involvement of RNF187 in germ cell development, we conducted interference and overexpression assays using GC-2 cells, a mouse spermatocyte-derived cell line. Our findings reveal that the interaction between RNF187 and histone H3 increases the viability, proliferation, and migratory capacity of GC-2 cells. Moreover, we provide evidence demonstrating that RNF187 interacts with H3 and mediates the ubiquitination of H3 at lysine 57 (K57) or lysine 80 (K80), directly or indirectly resulting in increased cellular transcription. This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediating histone H3 ubiquitination, thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of gene transcription. These discoveries provide a new theoretical foundation for further comprehensive investigations into the function of RNF187 in the reproductive system.

E3 ubiquitin ligase RNF187 promotes growth of spermatogonia via lysine 48-linked polyubiquitination-mediated degradation of KRT36/KRT84.

Ubiquitination is the most common post-translational modification and is essential for various cellular regulatory processes. RNF187, which is known as RING domain AP1 coactivator-1, is a member of the RING finger family. RNF187 can promote the proliferation and migration of various tumor cells. However, whether it has a similar role in regulating spermatogonia is not clear. This study explored the role and molecular mechanism of RNF187 in a mouse spermatogonia cell line (GC-1). We found that RNF187 knockdown reduced the proliferation and migration of GC-1 cells and promoted their apoptosis. RNF187 overexpression significantly increased the proliferation and migration of GC-1 cells. In addition, we identified Keratin36/Keratin84 (KRT36/KRT84) as interactors with RNF187 by co-immunoprecipitation and mass spectrometry analyses. RNF187 promoted GC-1 cell growth by degrading KRT36/KRT84 via lysine 48-linked polyubiquitination. Subsequently, we found that KRT36 or KRT84 overexpression significantly attenuated proliferation and migration of RNF187-overexpressing GC-1 cells. In summary, our study explored the involvement of RNF187 in regulating the growth of spermatogonia via lysine 48-linked polyubiquitination-mediated degradation of KRT36/KRT84. This may provide a promising new strategy for treating infertility caused by abnormal spermatogonia development.