Keratoconus is a bilateral ocular condition characterized by irregularities and the thinning of the cornea. Decreased central corneal thickness is a hallmark of the condition, and numerous genes have played a role in altering corneal thickness and the subsequent development of keratoconus. Variants in the structural and regulatory genes of the extracellular matrix have been highly associated with keratoconus, as well as with pectus excavatum, a chest wall deformity commonly seen in connective tissue disorders. This report describes a patient with a c.1720-11T>A intronic variant in the collagen-encoding gene, COL5A1, who was diagnosed with early-onset keratoconus and demonstrated a significant pectus excavatum. This report associates a COL5A1 variant with these seemingly unrelated phenotypic associations, further advancing the literature on the topic.

This is a case of a 46-year-old woman who presented with right common iliac artery dissection preceded by a left common iliac artery dissection and rupture 6 years earlier. Both iliac arteries required repair. Based on her presentation, she met the clinical diagnostic criteria for vascular Ehlers-Danlos syndrome; however, the genetic workup demonstrated that she had classic Ehlers-Danlos syndrome due to a null variant in COL5A1, which is rarely associated with arteriopathy.

UNASSIGNED: We aimed to screen and construct a predictive model for pregnancy loss in polycystic ovary syndrome (PCOS) patients through machine learning methods.
UNASSIGNED: We obtained the endometrial samples from 33 PCOS patients and 7 healthy controls at the Reproductive Center of the Second Hospital of Lanzhou University from September 2019 to September 2020. Liquid chromatography tandem mass spectrometry (LCMS/MS) was conducted to identify the differentially expressed proteins (DEPs) of the two groups. Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to analyze the related pathways and functions of the DEPs. Then, we used machine learning methods to screen the feature proteins. Multivariate Cox regression analysis was also conducted to establish the prognostic models. The performance of the prognostic model was then evaluated by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). In addition, the Bootstrap method was conducted to verify the generalization ability of the model. Finally, linear correlation analysis was performed to figure out the correlation between the feature proteins and clinical data.
UNASSIGNED: Four hundred and fifty DEPs in PCOS and controls were screened out, and we obtained some pathways and functions. A prognostic model for the pregnancy loss of PCOS was established, which has good discrimination and generalization ability based on two feature proteins (TIA1, COL5A1). Strong correlation between clinical data and proteins were identified to predict the reproductive outcome in PCOS.
UNASSIGNED: The model based on the TIA1 and COL5A1 protein could effectively predict the occurrence of pregnancy loss in PCOS patients and provide a good theoretical foundation for subsequent research.

In recent years, the nexus between genetics and biomechanics has garnered significant attention, elucidating the role of genomic determinants in shaping the biomechanical attributes of human joints, specifically the knee. This review seeks to provide a comprehensive exploration of the molecular basis underlying knee joint locomotor function. Leveraging advancements in genomic sequencing, we identified specific genetic markers and polymorphisms tied to key biomechanical features of the knee, such as ligament elasticity, meniscal resilience, and cartilage health. Particular attention was devoted to collagen genes like COL1A1 and COL5A1 and their influence on ligamentous strength and injury susceptibility. We further investigated the genetic underpinnings of knee osteoarthritis onset and progression, as well as the potential for personalized rehabilitation strategies tailored to an individual\'s genetic profile. We reviewed the impact of genetic factors on knee biomechanics and highlighted the importance of personalized orthopedic interventions. The results hold significant implications for injury prevention, treatment optimization, and the future of regenerative medicine, targeting not only knee joint health but joint health in general.

This meta-analysis aimed to investigate the association between genetic polymorphisms in Collagen type 1 alpha-1 (COL1A1), Collagen type 3 alpha-1 (COL3A1), Collagen type 5 alpha-1 (COL5A1), and Collagen type 12 alpha-1 (COL12A1) genes and anterior cruciate ligament (ACL) injuries in athletes. A systematic search was diligently conducted on the PubMed and Web of Science databases to identify relevant studies on 5-9 September 2023. Only case-control studies were included in the meta-analysis. A total of 19 studies were reviewed, involving the analysis of 3522 cases and 6399 control subjects. Data relevant to the study objectives were extracted from these chosen studies and subsequently analyzed using either a random-effects or fixed-effects model. It indicates that individuals carrying the G allele in the COL1A1 (rs1107946) gene have a decreased risk of anterior cruciate ligament injuries (OR: -0.27, 95% CI: -0.42 to -0.12, p < 0.001). A similar relationship was observed in the dominant model, but this relationship was reversed in the recessive model (OR: 0.69, 95% CI: 0.33 to 1.05, p < 0.001). However, no significant associations were found in the COL3A1 (rs1800255) and COL5A1 (rs12722) genes. In the COL12A1 (rs970547) gene, the A allele was associated with an increased risk of anterior cruciate ligament injuries (OR: 0.18, 95% CI: 0.01 to 0.36, p = 0.041). This meta-analysis suggests that genetic variants in COL1A1 (rs1107946) and COL12A1 (rs970547) may be associated with ACL injuries in athletes. However, COL3A1 rs1800255 and COL5A1 rs12722 gene variants do not appear to have a significant association with these injuries.

Osteoarthritis (OA) is a non-inflammatory degenerative joint disease, characterized by joint pain and stiffness. The prevalence of OA increases with age. However, the relationship between biomarkers [collagen type III α1 (COL3A1), COL5A1, COL6A2, COL12A1] and OA remains unclear. The OA subchondral bone dataset GSE51588 was downloaded from the GEO database, and the differentially expressed genes (DEGs) were screened. Weighted gene co-expression network analysis was performed, and a protein-protein interaction network was constructed and further analyzed using Cytoscape and STRING. Functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and then Gene Set Enrichment Analysis (GSEA) was used to formulate the molecular functions and pathways based on the results of GO and KEGG analyses. Comparative Toxicogenomics Database and TargetScan were used to identify the hub-gene-related diseases and the microRNAs that regulated the central hub genes. Immunohistochemical staining was performed to confirm the expression of related proteins in OA and non-OA tissue samples. A total of 1,679 DEGs were identified. GO analysis showed that the DEGs were primarily enriched in the process of \'immune system\', \'extracellular region\', \'secretory granule\', \'collagen-containing extracellular matrix\', \'ECM-receptor, glycosaminoglycan binding\' and \'systemic lupus erythematosus\'. The results of GSEA were similar to those of GO and KEGG enrichment terms for DEGs. A total of 25 important modules were generated, and two core gene clusters and seven core genes were obtained (COL6A2, COL5A2, COL12A1, COL5A1, COL6A1, LUM and COL3A1). Core genes were expressed differentially between OA subchondral bone and normal tissue samples. The expression levels of COL3A1, COL5A1 and COL6A2 in OA subchondral bone tissue were higher compared with those in normal tissues, but COL12A1 expression was not significantly increased; all stained markers were highly expressed in surrounding tissues of immunohistochemical staining. In conclusion, COL3A1, COL5A1 and COL6A2 may be potential molecular biomarkers for OA.

BACKGROUND: Aberrant expression of collagen type V alpha 1 chain (COL5A1) has been linked to several forms of human cancers. In this work, we focused on the interaction of the LINC00173/GATA binding protein 6 (GATA6)/COL5A1 axis in the malignant property of oral squamous cell carcinoma (OSCC) cells.
METHODS: We analyzed six publicly accessible datasets GSE160042, GSE74530, GSE138206, GSE23558, GSE31853 and GSE146483 to identify aberrantly expressed genes in OSCC. The expression of COL5A1 in OSCC tissues and cell lines was examined by reverse transcription-quantitative polymerase chain reaction and/or immunohistochemistry. The regulatory mechanism responsible for COL5A1 transcription was predicted via bioinformatics systems, and the interactions of LINC00173, GATA6, and COL5A1 were identified by immunoprecipitation and luciferase assays. Overexpression or downregulation of COL5A1, GATA6, and LINC00173 were induced in OSCC cell lines to determine their roles in the malignant phenotype of the OSCC cells in vitro and in vivo.
RESULTS: COL5A1 showed elevated expression in OSCC tissues and cells. The COLA51 knockdown suppressed proliferation, migration and invasiveness, apoptosis resistance, and pro-angiogenic ability of OSCC cells, and it suppressed the growth and dissemination of xenograft tumors in vivo. GATA6 bound to COL5A1 promoter to activate its transcription, whereas LINC00173 bound to GATA6 to block this transcriptional activation. Overexpression of GATA6 or COL5A1 promoted the malignant phenotype of the OSCC cells, which were blocked upon LINC00173 upregulation.
CONCLUSIONS: This work demonstrates that LINC00173 blocks GATA6-mediated transcription of COL5A1 to affect malignant development of OSCC.

Single-nucleotide polymorphisms (SNPs) in collagen genes are predisposing factors for anterior cruciate ligament (ACL) rupture. Although these events are more frequent in females, the sex-specific risk of reported SNPs has not been evaluated.
We aimed to assess the sex-specific risk of historic non-contact ACL rupture considering candidate SNPs in genes previously associated with muscle, tendon, ligament and ACL injury in elite footballers.
This was a cohort genetic association study.
Forty-six (twenty-four females) footballers playing for the first team of FC Barcelona (Spain) during the 2020-21 season were included in the study. We evaluated the association between a history of non-contact ACL rupture before July 2022 and 108 selected SNPs, stratified by sex. SNPs with nominally significant associations in one sex were then tested for their interactions with sex on ACL.
Seven female (29%) and one male (4%) participants had experienced non-contact ACL rupture during their professional football career before the last date of observation. We found a significant association between the rs13946 C/C genotype and ACL injury in women footballers (p = 0.017). No significant associations were found in male footballers. The interaction between rs13946 and sex was significant (p = 0.027). We found that the C-allele of rs13946 was exclusive to one haplotype of five SNPs spanning COL5A1.
The present study suggests the role of SNPs in genes encoding for collagens as female risk factors for ACL injury in football players.
The genetic profiling of athletes at high risk of ACL rupture can contribute to sex-specific strategies for injury prevention in footballers.

Long noncoding RNAs (lncRNAs) are known to participate in the progression of several cancers, including esophageal carcinoma (EC), a common malignancy of the digestive system. Although the role of the lncRNA-miRNA-mRNA regulatory network is crucial for the growth and progression of EC, the regulation of lncRNA BBOX1-AS1 (BBOX1 antisense RNA1) remains unclear. We performed reverse transcription-quantitative PCR (RT-qPCR) and western blotting to evaluate miR-361-3p, collagen type V alpha 1 chain (COL5A1), and BBOX1-AS1 expression levels in EC cells and tissues. The colony formation assay (CFA) and Cell Counting Kit-8 (CCK-8) were employed to identify EC cell proliferation, while western blotting was used to examine EC cell apoptosis and Bax and Bcl-2 expression levels. The effect of BBOX1-AS1 on EC proliferation was determined using an in vivo carcinogenesis assay. Correlation between COL5A1, BBOX1-AS1, and miR-361-3p was examined using the luciferase reporter system and RNA immunoprecipitation assay (RIP). Herein, we observed that BBOX1-AS1 expression levels were upregulated in EC cells and tissues. BBOX1-AS1 knockdown inhibited EC cell proliferation and conferred a pro-apoptotic effect. These results indicated a positive interaction between BBOX1-AS1 and miR-361-3p in EC and a negative association with miR-361-3p. COL5A1 was recognized as a downstream miR-361-3p target and was inversely related to miR-361-3p in EC. Therefore, BBOX1-AS1 expression suppressed cell apoptosis and promoted cell proliferation via the downregulation of miR-361-3p and upregulation of COL5A1 expression. Overall, BBOX1-AS1 facilitates EC progression via the miR-361-3p or COL5A1 axis, indicating that BBOX1-AS1 might be a potential therapeutic target for EC therapy.

UNASSIGNED: Laryngeal squamous cell cancer (LSCC) is a highly malignant tumor originating from the respiratory system. Circular RNAs have been reported to be associated with the treatment and prognosis of a variety of cancers, including LSCC.
UNASSIGNED: The expression of circBFAR, miR-31-5p, and collagen type V alpha 1 chain (COL5A1) in LSCC tissues and cells was detected by quantitative real-time polymerase chain reaction. Cell counting kit 8 and 5-Ethynyl-2\'-deoxyuridine assays were used to detect cell proliferation. Wound healing assay and transwell assay were used to test cell migration and invasion, respectively. The protein expression in LSCC cells was detected with western blot. The relationships between miR-31-5p and circBFAR or COL5A1 were identified by dual-luciferase reporter assay, RNA-pull down assay, and immunoprecipitation assay. The effect of circBFAR on tumor growth in vivo was detected by tumor xenograft mice experiment. The protein expression of COL5A1 and KI-67 in LSCC tissues was measured by immunohistochemistry assay.
UNASSIGNED: CircBFAR was increased in LSCC tissues and cells, and was related to advanced clinical stage and overall survival of LSCC patients. The cell viability and proliferation were inhibited by circBFAR knockdown and silencing of circBFAR blocked migration and invasion of LSCC cells. CircBFAR knockdown suppressed cell tube formation, and the protein expression of KI-67, matrix metallopeptidase 2 (MMP2), and vascular endothelial growth factor A (VEGFA) in LSCC cells. MiR-31-5p was the target of circBFAR, and the inhibitory effects of circBFAR deficiency on viability, proliferation, migration, invasion, tube formation and the protein expression of KI-67, MMP2, and VEGFA in LSCC cells were rescued by miR-31-5p downregulation. COL5A1 was negatively regulated by miR-31-5p, and was boosted in LSCC tissues and cells. COL5A1 overexpression reversed the inhibitory effects of miR-31-5p on LSCC cells. CircBFAR insufficiency hindered tumor growth in vivo.
UNASSIGNED: CircBFAR, miR-31-5p, and COL5A1 in LSCC progression might provide novel therapeutic targets for LSCC clinical intervention.