ITGA3 participates in the pathogenesis of recurrent spontaneous abortion by downregulating ULK1-mediated autophagy to inhibiting trophoblast function.

Recurrent spontaneous abortion (RSA) is a significant challenge encountered by couples of reproductive ages, with inadequate trophoblast invasion identified as a primary factor in RSA pathogenesis. However, the precise molecular mechanisms through which trophoblast cells dysfunction leads to RSA remain incompletely understood. Research has highlighted the critical role of integrins in embryo implantation and development. While integrin α-3 (ITGA3) is recognized for its promotion of invasion in cancer cells, its involvement in miscarriage remains poorly characterized. This investigation initially assessed ITGA3 expression in villous tissues obtained from RSA patients and induced abortion patients. The findings demonstrated a notable reduction in ITGA3 levels in the villous tissues of RSA patients compared control group. Subsequent in vitro analyses indicated that ITGA3 knockdown inhibited the migration, invasion, and proliferation of trophoblast cells. Through RNA sequencing and subsequent experimentation, it was revealed that ITGA3 regulated ULK1-mediated autophagy to influence trophoblast cells invasion, migration, and proliferation. Furthermore, utilizing a miscarriage animal model, the diminished expression of ITGA3 and ULK1 in the placentas of RSA mice was confirmed. In conclusion, the study findings suggest that the downregulation of ITGA3 suppresses ULK1 expression, consequently impeding autophagy to initiation and impeding trophoblast cells invasion and migration, thereby contributing to the pathological progression of RSA.

MUC1 promotes cervical squamous cell carcinoma through ERK phosphorylation-mediated regulation of ITGA2/ITGA3.

In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA2/3, in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future.

MUC1 is overexpressed in cervical squamous cell carcinoma. MUC1 regulates ERK phosphorylation, and subsequently upregulates ITGA2 and ITGA3 expression to promote tumorigenesis in cervical squamous cell carcinoma. A combination drug regimen targeting MUC1 and ERK achieved better results compared than MUC1 alone.

ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis.

Contribution of integrin superfamily genes to treatment resistance remains uncertain. Genome patterns of thirty integrin superfamily genes were analyzed of using bulk and single-cell RNA sequencing, mutation, copy number, methylation, clinical information, immune cell infiltration, and drug sensitivity data. To select the integrins that are most strongly associated with treatment resistance in pancreatic cancer, a purity-independent RNA regulation network including integrins were constructed using machine learning. The integrin superfamily genes exhibit extensive dysregulated expression, genome alterations, epigenetic modifications, immune cell infiltration, and drug sensitivity, as evidenced by multi-omics data. However, their heterogeneity varies among different cancers. After constructing a three-gene (TMEM80, EIF4EBP1, and ITGA3) purity-independent Cox regression model using machine learning, ITGA3 was identified as a critical integrin subunit gene in pancreatic cancer. ITGA3 is involved in the molecular transformation from the classical to the basal subtype in pancreatic cancer. Elevated ITGA3 expression correlated with a malignant phenotype characterized by higher PD-L1 expression and reduced CD8+ T cell infiltration, resulting in unfavorable outcomes in patients receiving either chemotherapy or immunotherapy. Our findings suggest that ITGA3 is an important integrin in pancreatic cancer, contributing to chemotherapy resistance and immune checkpoint blockade therapy resistance.

lncRNA ITGB8-AS1 functions as a ceRNA to promote colorectal cancer growth and migration through integrin-mediated focal adhesion signaling.

Long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis and progression of colorectal cancer (CRC). However, functions of most lncRNAs in CRC and their molecular mechanisms remain uncharacterized. Here we found that lncRNA ITGB8-AS1 was highly expressed in CRC. Knockdown of ITGB8-AS1 suppressed cell proliferation, colony formation, and tumor growth in CRC, suggesting oncogenic roles of ITGB8-AS1. Transcriptomic analysis followed by KEGG analysis revealed that focal adhesion signaling was the most significantly enriched pathway for genes positively regulated by ITGB8-AS1. Consistently, knockdown of ITGB8-AS1 attenuated the phosphorylation of SRC, ERK, and p38 MAPK. Mechanistically, ITGB8-AS1 could sponge miR-33b-5p and let-7c-5p/let-7d-5p to regulate the expression of integrin family genes ITGA3 and ITGB3, respectively, in the cytosol of cells. Targeting ITGB8-AS1 using antisense oligonucleotide (ASO) markedly reduced cell proliferation and tumor growth in CRC, indicating the therapeutic potential of ITGB8-AS1 in CRC. Furthermore, ITGB8-AS1 was easily detected in plasma of CRC patients, which was positively correlated with differentiation and TNM stage, as well as plasma levels of ITGA3 and ITGB3. In conclusion, ITGB8-AS1 functions as a competing endogenous RNA (ceRNA) to regulate cell proliferation and tumor growth of CRC via regulating focal adhesion signaling. Targeting ITGB8-AS1 is effective in suppressing CRC cell growth and tumor growth. Elevated plasma levels of ITGB8-AS1 were detected in advanced-stage CRC. Thus, ITGB8-AS1 could serve as a potential therapeutic target and circulating biomarker in CRC.

FTO Knockdown-Mediated Maturation of miR-383-5p Inhibits Malignant Advancement of Pancreatic Cancer by Targeting ITGA3.

m6A demethylase FTO is confirmed to be involved in pancreatic cancer progression. FTO regulates miRNA processing. To investigate the regulatory effect of FTO on miR-383-5p and its role in pancreatic cancer. The expression of miR-383-5p, ITGA3, and FTO was predicted using bioinformatic analysis in tissues and was measured using qPCR in cells. Cell biological functions were investigated using MTT assay, Transwell assay, sphere formation assay, and qPCR. The targeting relationship between miR-383-5p and ITGA3 was evaluated using the dual-luciferase reporter assay. The effect of FTO on miR-383-5p processing was evaluated using RIP and MeRIP assay. FTO expression was upregulated in pancreatic cancer and silencing of FTO promoted the processing of miR-383-5p in an m6A-dependent manner. m6A-modified miRNA processing was recognized by IGF2BP1. Downregulation of miR-383-5p reversed FTO knockdown-induced inhibition of cellular processes. The FTO/miR-383-5p/ITGA3 axis facilitated cell viability, metastasis, and stemness in pancreatic cancer.

Zebrafish integrin a3b is required for cardiac contractility and cardiomyocyte proliferation.

In cardiac muscle cells, heterodimeric integrin transmembrane receptors are known to serve as mechanotransducers, translating mechanical force to biochemical signaling. However, the roles of many individual integrins have still not been delineated. In this report, we demonstrate that Itga3b is localized to the sarcolemma of cardiomyocytes from 24 to 96 hpf. We further show that heterozygous and homozygous itga3b/bdf mutant embryos display a cardiomyopathy phenotype, with decreased cardiac contractility and reduced cardiomyocyte number. Correspondingly, proliferation of ventricular and atrial cardiomyoctyes and ventricular epicardial cells is decreased in itga3b mutant hearts. The contractile dysfunction of itga3b mutants can be attributed to cardiomyocyte sarcomeric disorganization, including thin myofilaments with blurred and shortened Z-discs. Together, our results reveal that Itga3b localizes to the myocardium sarcolemma, and it is required for cardiac contractility and cardiomyocyte proliferation.

Detection of bladder cancer with aberrantly fucosylated ITGA3.

We describe a simple, non-invasive assay to identify fucosylated-glycoisoform of integrin alpha-3 (ITGA3) directly from unprocessed urine. ITGA3 was detected directly from the urine of bladder cancer (BlCa) (n = 13) and benign prostatic hyperplasia (BPH) (n = 9) patients with the use of lectins coated on europium-doped-nanoparticles (Eu3+-NPs). Lectin Ulex europaeus agglutinin-I (UEA) showed enhanced binding with BlCa-derived ITGA3. The evaluation with individual samples showed that a glycovariant ITGA3-UEA assay could significantly discriminate BlCa from BPH patients (p = 0.007). The detection of aberrantly fucosylated-isoform of ITGA3 from urine can be used to distinguish BlCa from age-matched benign controls in a simple sandwich assay.

Interference with circBC048201 inhibits the proliferation, migration, and invasion of bladder cancer cells through the miR-1184/ITGA3 axis.

The abnormal expression of circular RNA (circRNA) is bound up with the progress of various human cancers. This study aimed to reveal the potential role and mechanism of circBC048201 in the proliferation, migration, and invasion of bladder cancer cells. Quantitative real-time PCR was performed to detect the expression of circBC048201. Cell Counting Kit-8, colony formation, and transwell migration and invasion assays were used to confirm the in vitro functions of circBC048201. Western blot, RNA pull-down, and dual-luciferase reporter gene experiments were performed to study the potential mechanism. circBC048201 was abnormally highly expressed in bladder cancer tissues and cells, and the interference with circBC048201 inhibited bladder cancer cell proliferation, migration, and invasion. From the potential mechanism analysis, our data suggested that circBC048201 and miR-1184, miR-1184 and ITGA3 could bind to each other, and the interference with circBC048201 repressed bladder cancer cell proliferation, migration, and invasion through the miR-1184/ITGA3 axis. In summary, our results showed that circBC048201 was abnormally highly expressed in bladder cancer tissues and cells, and the interference with circBC048201 inhibited the proliferation, migration, and invasion of bladder cancer cells through the miR-1184/ITGA3 axis.

MicroRNA-524-5p suppresses the progression of papillary thyroid carcinoma cells via targeting on FOXE1 and ITGA3 in cell autophagy and cycling pathways.

MicroRNAs are beneficial for cancer therapy as they can simultaneously downregulate multiple targets involved in diverse biological pathways related to tumor development. In papillary thyroid cancer, many microRNAs were identified as differentially expressed factors in tumor tissues. In another way, recent studies revealed cell proliferation, cell cycling, apoptosis, and autophagy are critical pathways controlling papillary thyroid cancer development and progression. As miR-524-5p was approved as a cancer suppressor targeting multiple genes in several types of cancer cells, this study aims to characterize the role of miR-524-5p in the thyroid cancer cell. The expression of miR-524-5p was decreased in the papillary thyroid cancer tissues and cell lines, while forkhead box E1 (FOXE1) and ITGA3 were increased. In the clinical case, expression of miR-524-5p, FOXE1, and ITGA3 were significantly correlated with papillary thyroid cancer development and progression. FOXE1 and ITGA3 were approved as direct targets of miR-524-5p. miR-524-5p could inhibit papillary thyroid cancer cell viability, migration, invasion, and apoptosis through targeting FOXE1 and ITGA3. Cell cycling and autophagy pathways were disturbed by downregulation of FOXE1 and ITGA3, respectively. Collectively, miR-524-5p targeting on FOXE1 and ITGA3 prevents thyroid cancer progression through different pathways including cell cycling and autophagy.

Regulation of ITGA3 by the anti-tumor miR-199 family inhibits cancer cell migration and invasion in head and neck cancer.

For patients with head and neck squamous cell carcinoma (HNSCC), survival rates have not improved due to local recurrence and distant metastasis. Current targeted molecular therapies do not substantially benefit HNSCC patients. Therefore, it is necessary to use advanced genomic approaches to elucidate the molecular mechanisms underlying the aggressiveness of HNSCC cells. Analysis of our microRNA (miRNA) expression signature by RNA sequencing showed that the miR-199 family (miR-199a-5p, miR-199a-3p, miR-199b-5p and miR-199b-3p) was significantly reduced in cancer tissues. Ectopic expression of mature miRNA demonstrated that all members of the miR-199 family inhibited cancer cell migration and invasion by HNSCC cell lines (SAS and HSC3). These findings suggested that both passenger strands and guide strands of miRNA are involved in cancer pathogenesis. In silico database and genome-wide gene expression analyses revealed that the gene coding for integrin α3 (ITGA3) was regulated by all members of the miR-199 family in HNSCC cells. Knockdown of ITGA3 significantly inhibited cancer cell migration and invasion by HNSCC cells. Moreover, overexpression of ITGA3 was confirmed in HNSCC specimens, and high expression of ITGA3 predicted poorer survival of the patients (P = 0.0048). Our data revealed that both strands of pre-miR-199a (miR-199a-5p and miR-199a-3p) and pre-miR-199b (miR-199b-5p and miR-199b-3p) acted as anti-tumor miRNA in HNSCC cells. Importantly, the involvement of passenger strand miRNA in the regulation of cellular processes is a novel concept in RNA research. Novel miRNA-based approaches for HNSCC can be used to identify potential targets for the development of new therapeutic strategies.

Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer.

Analysis of microRNA (miRNA) expression signatures in prostate cancer (PCa) and castration-resistant PCa has revealed that miRNA-223 is significantly downregulated in cancer tissues, suggesting that miR-223 acts as a tumor-suppressive miRNA by targeting oncogenes. The aim of this study was to investigate the functional roles of miR-223 and identify downstream oncogenic targets regulated by miR-223 in PCa cells. Functional studies of miR-223 were carried out to investigate cell proliferation, migration, and invasion using PC3 and PC3M PCa cell lines. Restoration of miR-223 significantly inhibited cancer cell migration and invasion in PCa cells. In silico database and genome-wide gene expression analyses revealed that ITGA3 and ITGB1 were direct targets of miR-223 regulation. Knockdown of ITGA3 and ITGB1 significantly inhibited cancer cell migration and invasion in PCa cells by regulating downstream signaling. Moreover, overexpression of ITGA3 and ITGB1 was observed in PCa clinical specimens. Thus, our data indicated that downregulation of miR-223 enhanced ITGA3/ITGB1 signaling and contributed to cancer cell migration and invasion in PCa cells. Elucidation of the molecular pathways modulated by tumor-suppressive miRNAs provides insights into the mechanisms of PCa progression and metastasis.

Proteomic and functional investigation of the colon cancer relapse-associated genes NOX4 and ITGA3.

Colon cancer is a major cause of cancer-related deaths worldwide. Adjuvant chemotherapy significantly reduces mortality in stage III colon cancer; however, it is only marginally effective in stage II patients. There is also increasing evidence that right-side colon cancer is different from left-side colon cancer. We have observed that the genes altered in expression between the poor and good prognosis tumors vary significantly depending on whether the malignancy originates on the right or left side of the colon. We have identified NADPH oxidase 4 (NOX4) to be highly predictive of relapse in stage II left-side colon cancer, whereas integrin alpha 3 beta 1 (ITGA3) is predictive of relapse in stage II right-side colon cancer. To investigate the underlying molecular mechanisms, we are analyzing the effect of ITGA3 and NOX4 silencing via RNA interference and pharmacological inhibition on global protein expression patterns via iTRAQ labeling and mass spectrometry in colon cancer cells. On the basis of bioinformatic analysis, the functions of these genes were assessed through phenotypic assays, revealing roles in cell migration and reactive oxygen species generation. These biomarkers for relapse risk are of clinical interest and lead to insight into how a tumor progresses to metastasis.

Identifying the prognosis implication, immunotherapy response prediction value, and potential targeted compound inhibitors of integrin subunit α3 (ITGA3) in human cancers.

The integrin subunit α3 (ITGA3) is a member of the integrin alpha chain protein family, which could promote progression, metastasis, and invasion in some cancers. Still, its function in the tumor microenvironment (TME), cancer prognosis, and immunotherapy remains unclear. A multifaceted analysis of ITGA3 in pan-cancer utilizing various databases and online web tools revealed ITGA3 was aberrantly expressed in tumor tissues and upregulated in most cancers, which may be related to ITGA3 genomic alterations and methylation modification. In addition, ITGA3 was significantly correlated with the poor or better prognosis of cancer patients, immune-related pathways in hallmark, immune infiltration, and immune checkpoints, revealing a biological function of ITGA3 in the tumor progression, tumor microenvironment, and tumor immunity. We also found that ITGA3 could predict the response to tumor immunotherapy based on cytokine-treated samples and immunotherapy cohorts. ITGA3 may participate in shaping and regulating the tumor microenvironment to affect the tumor immune response, which was a promising immunotherapy response predictive biomarker and potential therapeutic target to work synergistically with cancer immunotherapy to boost the response and efficacy. Finally, potential targeted compound inhibitors and sensitive drugs were screened using databases ConnectivityMap (CMap) and CellMiner, and AutoDock Tools was used for molecular docking.

Integrin α3 Mediates Stemness and Invasion of Glioblastoma by Regulating POU3F2.

BACKGROUND: Glioblastoma (GBM) is an aggressive brain tumor. Integrins have been implicated in the malignancy of GBM. A recent study demonstrated that integrin α3 (ITGA3) promoted the invasion of breast cancer cells by regulating transcriptional factor POU3F2. However, whether this also happened in GBM remained unknown. METHODS: Therefore, we explored the relationship between ITGA3 and POU3F2 in GBM. We measured the expression of ITGA3 and POU3F2 in GBM tissues. We generated ITGA3 knockdown and POU3F2 knockdown GBM U87MG cells and the proliferation, migration and invasion, the expression of stemness markers and epithelial to mesenchymal transition (EMT) markers were measured. We transplanted ITGA3 knockdown and POU3F2 knockdown GBM U87MG cells into mice. The mice were treated with anti-ITGA3 antibody. The tumor sizes, the expression of stemness markers and epithelial-to-mesenchymal transition (EMT) markers were measured. RESULTS: Both ITGA3 and POU3F2 were upregulated in GBM tissues. Knocking down ITGA3 resulted in reduced expression of POU3F2. Knocking down ITGA3 and POU3F2 suppressed U87MG cells proliferation, migration and invasion, inhibited the expression of stemness markers and prevented epithelial- to-mesenchymal transition. The transplantation of ITGA3 knockdown and POU3F2 knockdown U87MG cells decreased tumor size. CONCLUSION: Anti-ITGA3 antibody treatment reduced the tumor size. ITGA3 regulates stemness and invasion of glioblastoma through POU3F2.

CD9 and ITGA3 are regulated during HIV-1 infection in macrophages to support viral replication.

Monocytes/macrophages are important target cells for HIV-1. Here, we investigated whether HIV-1 induces changes in the macrophage gene expression profile to support viral replication. We observed that the macrophage gene expression profiles dramatically changed upon HIV-1 infection. The majority of the HIV-1 regulated genes were also differentially expressed in M2a macrophages. The biological functions associated with the HIV-1 induced gene expression profile in macrophages were mainly related to inflammatory responses. CD9 and ITGA3 were among the top genes upregulated upon HIV-1 infection. We showed that these genes support viral replication and that downregulation of these genes decreased HIV-1 replication in macrophages. Here we showed that HIV-1 infection of macrophages induces a gene expression profile that may dampen inflammatory responses. CD9 and ITGA3 were among the top genes regulated by HIV-1 and were shown to support viral production most likely at the level of viral budding and release.

ITGA3 Is Associated With Immune Cell Infiltration and Serves as a Favorable Prognostic Biomarker for Breast Cancer.

BACKGROUND: ITGA3 is a member of the integrin family, a cell surface adhesion molecule that can interact with extracellular matrix (ECM) proteins. The purpose of this study was to explore the significance of ITGA3 expression in the prognosis and clinical diagnosis of breast cancer patients. METHODS: Oncomine, the Human Protein Atlas (HPA) and UALCAN were used to analyze the expression of ITGA3 in various cancers. PrognoScan, GEPIA, Kaplan-Meier plotter and Easysurv were utilized to analyze the prognosis of ITGA3 in certain cancers. Based on TCGA data, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of ITGA3 expression. cBio-Portal and MethSurv were used to evaluate the genomic mechanism. LinkedOmics, NetworkAnalyst and Metascape were used to build the signaling network. TIMER is a web server for comprehensive analysis of tumor infiltrating immune cells and tumor infiltrating lymphocytes (TILs). RESULTS: The expression of ITGA3 in normal breast tissues was greater than that in breast cancer tissues at both the mRNA and protein levels. High expression of ITGA3 was associated with better prognosis of breast cancer patients. ROC analysis indicated that ITGA3 had significant diagnostic value. Genomic analysis revealed that promoter methylation of ITGA3 leads to transcriptional silencing, which may be one of the mechanisms underlying ITGA3 downregulation in BRCA. Immune infiltration analysis showed that ITGA3 may be involved in the recruitment of immune cells. CONCLUSIONS: This study identified ITGA3 as a novel biomarker to estimate the diagnosis and prognosis of breast cancer. In addition, ITGA3 is involved in ECM regulation and immune cell infiltration.

Expression and prognostic potential of PLEK2 in head and neck squamous cell carcinoma based on bioinformatics analysis.

BACKGROUND: PLEK2 (pleckstrin) could bind to membrane-bound phosphatidylinositols and further promote cell spread. Recently, several studies have noted the importance of PLEK2 in tumor metastasis. However, the role of PLEK2 in head and neck squamous cell carcinoma (HNSCC) remains to be elucidated. METHODS: The PLEK2 expression in HNSCC was identified using Oncomine, Gene Expression Omnibus (GEO), UALCAN databases, and western blot analysis. Prognosis analysis was performed using Kaplan-Meier plotter, DriverDBv3, UALCAN, UCSC Xena, and GEO databases. Single-cell functional analysis was further performed using the cancerSEA database. The PLEK2-related co-expressed genes were identified, and gene set enrichment analysis was performed using LinkedOmics. Furthermore, the top 10 hub genes were identified using the cytoHubba plug-in of Cytoscape. Then, gene enrichment analysis, pathway activity, and drug sensitivity analyses of the hub genes were performed using the R package "clusterProfiler" and GSCAlite. Finally, the UCSC Xena browser was utilized to explore the hub gene most likely to play a synergic role with PLEK2 in HNSCC. RESULTS: Elevated expression of PLEK2 was observed in HNSCC and even in HNSCC subgroups based on diverse clinicopathological features, portending a poor prognosis in HNSCC. PLEK2 was correlated with metastasis and hypoxia in HNSCC, and the PLEK2-related co-expressed genes were mainly involved in the focal adhesion pathway. The top 10 hub genes were primarily enriched in focal adhesion, HPV infection, ECM-receptor interaction, and PI3K-AKT signaling pathway, and epithelial-mesenchymal transition pathway was activated. Furthermore, the expression levels of the hub genes were associated with sensitivity and resistance to various small molecules and anti-cancer drugs. Further study suggested that ITGA3 and PLEK2 might be viewed as inextricably linked in facilitating HNSCC metastasis. CONCLUSIONS: In general, PLEK2 might serve as a potential biomarker for the diagnosis of HNSCC and guide the development of targeted therapies for HNSCC.

Evaluation of ITGA3 as a Biomarker of Progression and Recurrence in Papillary Thyroid Carcinoma.

OBJECTIVE: To investigate the expression of ITGA3 and its association with clinical outcomes in papillary thyroid carcinoma (PTC). METHODS: The expression level, association with clinicopathologic characteristics, co-expressed genes, signaling pathways of ITGA3 in thyroid cancer were comprehensively analyzed using bioinformatics analysis through multiple public gene databases. PTC specimens and cell lines were used to verify the results of bioinformatics analysis. RESULTS: Data mining based on the Oncomine database revealed that ITGA3 expression in classical PTC and tall cell variant PTC was much higher than that in normal thyroid tissue except the follicular variant PTC. Analysis based on The Cancer Genome Atlas (TCGA) database showed that the expression of ITGA3 varies greatly in pathological stages, pathological types, tumor invasion stages, and lymph node metastasis stages of thyroid carcinoma. High expression level of ITGA3 was correlated with tumor regional invasion and lymph node metastasis. Multivariate analysis using logistic regression model showed that high expression of ITGA3 was a risk factor that associated with PTC recurrence and lymph node metastasis. Survival analysis showed that patients with high expression of ITGA3 in PTC had a poorer relapse-free survival (RFS) than patients with low expression of ITGA3 (P < 0.05). Immunohistochemistry experiments showed that the expression of ITGA3 in recurrent thyroid cancer tissues was stronger than that in no-recurrent thyroid cancer tissues (P < 0.05). Knockdown of ITGA3 by sh-RNA in PTC cell lines suppresses cell viability and invasive and migrating capacity. CONCLUSION: ITGA3 is overexpressed in PTC, especially in those with higher tumor invasion grades and lymph node metastasis, and was associated with recurrence and poor RFS of PTC. High expression of ITGA3 may have the potential role of predicting PTC recurrence and lymph node metastasis.

A novel ITGA3 homozygous splice mutation in an ILNEB syndrome child with slow progression.

BACKGROUND AND AIMS: ILNEB (interstitial lung disease, nephrotic syndrome, epidermolysis bullosa) syndrome is caused by ITGA3 mutations. Demises usually happened at infancy. This study reports a complete ILNEB syndrome child with slow disease progression. MATERIALS AND METHODS: Clinical data and related specimens were collected. Genomic DNA was extracted for genetic sequencing. Integrin α3 expression was detected by western blotting and immunofluorescence staining. RESULTS: The patient was male. He experienced recurrent rashes shortly after birth. His sparse eyebrows and eyelashes gradually lost. The patient was vulnerable to respiratory infections and had recurrent fever after vaccine immunization after 4 years. He was found with nephrotic syndrome and polycystic renal dysplasia at 8 years and progressed to end-stage renal disease at 12 years. A chest Computed Tomography revealed intestinal lung disease at 8 years. Continuous oxygen supplementation was needed at 13 years. Counts of lymphocyte subsets revealed elevated percentage of double-negative T cells and activated T cells. Next-generation sequencing revealed a novel homozygous splice mutation c.2219 + 4A > Cin ITGA3 that was predicted to be deleterious. The mutation resulted in exon17 skipping with the loss of 80 bp in the mRNA. The aberrant integrin α3 mRNA level was lower compared to the healthy control. Integrin α3 protein was not detected in urine epithelial cells and skin of the patient. CONCLUSIONS: We report a patient harboring a novel ITGA3 homozygous splice mutation who presented with complete ILNEB syndrome but slow disease progression. Immune disorders were suspected.