Sertoli cells require hnRNPC to support normal spermatogenesis and male fertility in mice†.

Sertoli cells act as highly polarized testicular cells that nutritionally support multiple stages of germ cell development. However, the gene regulation network in Sertoli cells for modulating germ cell development has yet to be fully understood. In this study, we report that heterogeneous nuclear ribonucleoproteins C in Sertoli cells are essential for germ cell development and male fertility. Conditional knockout of heterogeneous nuclear ribonucleoprotein C in mouse Sertoli cells leads to aberrant Sertoli cells proliferation, disrupted cytoskeleton of Sertoli cells, and compromised blood-testis barrier function, resulting in loss of supportive cell function and, ultimately, defective spermiogenesis in mice. Further ribonucleic acid-sequencing analyses revealed these phenotypes are likely caused by the dysregulated genes in heterogeneous nuclear ribonucleoprotein C-deficient Sertoli cells related to cell adhesion, cell proliferation, and apoptotic process. In conclusion, this study demonstrates that heterogeneous nuclear ribonucleoprotein C plays a critical role in Sertoli cells for maintaining the function of Sertoli cells and sustaining steady-state spermatogenesis in mice.

Higher concentration of P7C3 than required for neuroprotection suppresses renal cell carcinoma growth and metastasis.

Background: P7C3 is a novel compound that has been widely applied in neurodegenerative diseases and nerve injury repair. Here, we show that higher concentrations of P7C3 than are required for in vivo neuroprotection have the novel function of suppressing renal cell carcinoma (RCC) proliferation and metastasis. Methods: Colony formation, CCK-8 and EdU assay were applied to evaluate RCC cell proliferation. Wound healing and transwell assay were used to measure RCC cell migration and invasion. Flow cytometry assay was employed to detect RCC cell apoptosis and cell cycle. qRT-PCR assay was carried out to measure ribonucleotide reductase subunit M2 (RRM2) mRNA expression level, while western blot assay was utilized to detect the expression level of target proteins. RCC cell growth in vivo was determined by xenografts in mice. Results: We observed that high concentrations of P7C3 could restrain the proliferation and metastasis of RCC cells and promote cell apoptosis. Mechanistically, this new effect of higher dose of P7C3 was associated with reduced expression of RRM2, and the beneficial efficacy of P7C3 in RCC was blocked when suppression of RRM2 was prevented. When RRM2 suppression was permitted, the cGAS-STING pathway was activated by virtue of RRM2/Bcl-2/Bax signaling. Lastly, intraperitoneal injection of this high level of P7C3 in mice potently inhibited tumor growth. Conclusion: In conclusion, we show here that P7C3 that exerts an anti-cancer effect in RCC. Our study indicated that P7C3 might act as a novel drug for RCC in the future. The regulatory signal pathway RRM2/Bcl-2/BAX/cGAS-STING might present novel insight to the potential mechanism of RCC development.

Erratum: A CRISPR Interference of CBP and p300 Selectively Induced Synthetic Lethality in Bladder Cancer Cells In Vitro: Erratum.

[This corrects the article DOI: 10.7150/ijbs.32332.].

[Retracted] miR­660­5p is associated with cell migration, invasion, proliferation and apoptosis in renal cell carcinoma.

Following the publication of the above article, the authors contacted the Editorial Office to explain that a couple of errors concerning data handling/labelling had been made, firstly during the preparation of the representative images in Fig. 3B, resulting in the wrong image being selected for the data panel showing the ACHN cells treated with 'Inhibitor NC' at 0 h experiment, and secondly in Fig. 5A, resulting in the wrong image being selected for the data panel showing the ACHN cells treated with 'Inhibitor NC' experiment. The authors requested that a corrigendum be published to take account of the errors that were made during the preparation of this figure. Subsequently, an independent investigation of the published data was undertaken by the Editorial Office, which revealed that the 'Inhibitor' data panel in Fig. 6A and the 'Mimic NC' data panel in Fig. 6B were also overlapping, such that these data were likely to have been derived from the same original source, even though these data panels were intended to have shown the results from differently performed experiments. The Editor of Molecular Medicine Reports has considered the authors' request to publish a corrigendum, but given the number of overlapping data panels that have been identified and the number of figures that would be in need of correction, the Editor has decided to decline the authors' request to publish a corrigendum on account of an overall lack of confidence in the presented data, and instead has determined that the paper should be retracted. Upon receiving this news from the Editor, the authors accepted the Editor's decision. The Editor apologizes to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 17: 2051­2060, 2018; DOI: 10.3892/mmr.2017.8052].

[Corrigendum] Identification of lncRNA EGOT as a tumor suppressor in renal cell carcinoma.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, concerrning the Transwell cell migration and invasion assay data shown in Fig. 6A and B for the 786­O cell line on p. 7206, the pcDNA3.1­EGOT 'Migration' and 'Invasion' (a­1 and b­1) data panels appeared to contain overlapping sections of data, such that they were potentially derived from the same original source, where these panels were intended to show the results from differently performed experiments. The authors have re­examined their original data, and realize that the 'Invasion' (b­1) panel in Fig. 6B was inadvertently chosen incorrectly. The revised version of Fig. 6, now featuring the correct data for the 'Invasion' experiment (B1 in the replacement figure) in Fig. 6B, is shown on the next page. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused.[Molecular Medicine Reports 16: 7072­7079, 2017; DOI: 10.3892/mmr.2017.7470].

[Corrigendum] MicroRNA­222­3p promotes tumor cell migration and invasion and inhibits apoptosis, and is correlated with an unfavorable prognosis of patients with renal cell carcinoma.

Following the publication of the above article, an interested reader drew to the attention of the Editorial Office that, in Fig. 3A on p. 530, two pairs of data panels were overlapping, such that certain of the panels appeared to have been derived from the same original sources where the results from differently performed experiments were intended to have been portrayed. The authors have examined their original data, and realize that errors associated with data handling/labelling during the preparation of the representative images in Fig. 3A had occurred. The revised version of Fig. 3, showing the correct data for the 'NC/ACHN/Invasion and Migration' data panels, the 'Inhibitor NC/786­O' panel and the 'Inhibitor NC/ACHN/Invasion' panel, is shown on the next page. The authors can confirm that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for giving them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 43: 525­534, 2019; DOI: 10.3892/ijmm.2018.3931].

N6-methyladenosine writer METTL16-mediated alternative splicing and translation control are essential for murine spermatogenesis.

BACKGROUND: The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. RESULTS: We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional knockout of Mettl16 in male mice impairs spermatogonial differentiation and meiosis initiation. Mechanistically, METTL16 interacts with splicing factors to regulate the alternative splicing of meiosis-related genes such as Stag3. Ribosome profiling reveals that the translation efficiency of many meiotic genes is dysregulated in METTL16-deficient testes. m6A-sequencing shows that ablation of METTL16 causes upregulation of the m6A-enriched transcripts and downregulation of the m6A-depleted transcripts, similar to Meioc and/or Ythdc2 mutants. Further in vivo and in vitro experiments demonstrate that the methyltransferase activity site (PP185-186AA) of METTL16 is necessary for spermatogenesis. CONCLUSIONS: Our findings support a molecular model wherein the m6A writer METTL16-mediated alternative splicing and translation efficiency regulation are required to control the mitosis-to-meiosis germ cell fate decision in mice, with implications for understanding meiosis-related male fertility disorders.

Changes in seminal plasma microecological dynamics and the mechanistic impact of core metabolite hexadecanamide in asthenozoospermia patients.

Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large-scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi-omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS-I), moderate AZS (AZS-II), and severe AZS (AZS-III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS-I) and an AZS group (AZS-II and AZS-III). Correlation and cross-reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium-Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite-targeting gene analysis and single-cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

In vitro chemokine (C-C motif) receptor 6-dependent non-inflammatory chemotaxis during spermatogenesis

BACKGROUND: Chemokine (C-C motif) receptor 6 (CCR6) is present in sperm and plays a significant role in sperm motility and chemotaxis acting in the reproductive tracts. However, the expression and functional significance of CCR6 in testis are still poorly understood, especially in the process of spermatogenesis. METHODS AND RESULTS: CCR6 was expressed in spermatogenic cell lines and its expression was shown in an age-dependent upregulation manner from puberty to adulthood in mouse testis. Immunostaining results confirmed the localization of CCR 6 in testis. Further chemotaxis assays demonstrated that spermatogenic cells GC-1 and -2 exhibited a directional movement toward CCR6-specific ligand such as CCL20 or Sertoli cells in vitro. CONCLUSIONS: The present findings indicate that CCR6 is involved in the chemotaxis of spermatogenic cells in vitro and promotes chemotaxis under non-inflammatory conditions during normal spermatogenesis.

Expression Profile of a Novel Germ Cell-specific Gene, TSCPA, in Mice and Human / 华中科技大学学报（医学）（英德文版）

In order to identify novel genes involved in spermatogenesis, testis cDNA samples from Balb/C mice of different postnatal days were hybridized with the whole mouse genome Affymetrix chip to screen the testis-specific genes. The characteristics of the selected genes were analyzed by RT-PCR as well as other bioinformatic tools. A novel differentially expressed testis-specific gene (GenBank Acces-sion No: NM_029042) in the developmental stages of testes was identified, and named TSCPA. Cellular mapping prediction of TSCPA indicated that its protein was probably expressed in nuclei, and one puta-tive domain (aa 332-377) was anchoring domain of cAMP-dependent type Ⅱ PK. The result of subcel-lular localization of GFP-TSCPA fusion protein in Cos-7 cells showed that TSCPA protein was ex-pressed in nuclei. RT-PCR analysis revealed that TSCPA was expressed specifically in mouse and hu-man testis. TSCPA gene was expressed weakly in 21-day-old mouse testis and the expression was in-creased gradually from 38th day to 6th month of mouse testes. No expression of hTSCPA was found in cryptorchidism and Sertoli-cell-only syndrome patients. It was concluded that the expression profile of TSCPA in human and mice indicated that TSCPA might play an important role in spermatogenesis.