This study was aimed to uncover the character and potential regulatory mechanism of EPB41L3 in cervical cancer (CC). CC cells were injected into BALB/c nude mice (female) to construct a xenograft tumor model. Real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were performed to evaluate the expression of EPB41L3, ERK/p38 MAPK signal markers in CC tissues and cells. Cell counting kit-8 (CCK-8) and Transwell was applied to analyze the viability, invasion, and migration of CC cell lines. EPB41L3 was substantially decreased both in CC tissues and cells. Cell viability, invasion, and migration of CC cells were reduced by overexpressing EPB41L3. Bioinformatics analysis prerdicted that EPB41L3 was strongly related to the ERK/p38 MAPK pathway. Compared with Ad-nc mice, the volume and weight of tumors and ERK/p38 MAPK signal markers were down-regulated in Ad-EPB41L3 mice. After knocking down EPB41L3 with EPB41L3 siRNA (siEPB41L3), the ERK/p38 MAPK pathway was activated. Moreover, SB203580 treatment reversed the effect of EPB41L3 silencing on the improvement in viability, migration, and invasion of CC cells. EPB41L3 suppresses the progression of CC via activating the ERK/p38 MAPK pathway. EPB41L3 may serve as an effective therapeutic target for CC.

OBJECTIVE: This meta-analysis aimed to comprehensively evaluate the diagnostic use of erythrocyte membrane protein band 4.1like3 (EPB41L3) methylation detection in cervical cancer (CC) and its precancerous lesions.
METHODS: CNKI, Wanfang, Cochrane Library, PubMed, and Ovid databases were searched using a combination of subject headings and free words. Pertinent data were retrieved after screening for inclusion and exclusion criteria, and the quality of the included studies was evaluated using QUADAS-2 criteria. The appropriate software was used for heterogeneity analysis and combined effect size calculation. Additionally, sensitivity analysis was used to evaluate the robustness of the combined results, and meta-regression and subgroup analysis were conducted to investigate the origins of heterogeneity.
RESULTS: This meta-analysis included six studies, including 525 healthy individuals, 182 cervical intraepithelial neoplasia 1 (CIN1) samples, 182 CIN2 samples, 281 CIN3 samples, and 226 CC samples. EPB41L3 methylation detection for CIN2 and above lesions demonstrated combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the curve of the comprehensive receiver operating characteristic curve of 0.67, 0.76, 3.19, 0.41, 7.60, and 0.80, respectively; CIN3 and above lesions demonstrated these evaluations at 0.73, 0.84, 4.35, 0.33, 23.94, and 0.90, respectively. Meta-regression analysis revealed that the population, time, sample type, detection method, literature quality, and sample size were not significant sources of heterogeneity affecting the combined diagnostic efficacy of CIN2 and above lesions (p > 0.05). Subgroup analysis revealed higher combined diagnostic values of CIN2 and above lesions in retrospective studies, tissue samples, and Chinese populations, with DORs of 41.03, 14.59, and 13.70, respectively.
CONCLUSIONS: EPB41L3 methylation demonstrated a relatively low diagnostic performance in CC and precancerous lesions. However, it merits further investigation as a potential biomarker. Integrating it with multiple gene detection, human papillomavirus testing, and ThinPrep liquid-based cytology test examination is recommended to explore improved diagnostic strategies for CC and its precancerous lesions.

Novel genetic and epigenetic factors involved in the development and prognosis of idiopathic pulmonary fibrosis (IPF) have been identified. We previously observed that erythrocyte membrane protein band 4.1-like 3 (EPB41L3) increased in the lung fibroblasts of IPF patients. Thus, we investigated the role of EPB41L3 in IPF by comparing the EPB41L3 mRNA and protein expression of lung fibroblast between patients with IPF and controls. We also investigated the regulation of epithelial-mesenchymal transition (EMT) in an epithelial cell line (A549) and fibroblast-to-myofibroblast transition (FMT) in a fibroblast cell line (MRC5) by overexpressing and silencing EPB41L3. EPB41L3 mRNA and protein levels, as measured using RT-PCR, real-time PCR, and Western blot, were significantly higher in fibroblasts derived from 14 IPF patients than in those from 10 controls. The mRNA and protein expression of EPB41L3 was upregulated during transforming growth factor-β-induced EMT and FMT. Overexpression of EPB41L3 in A549 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of N-cadherin and COL1A1. Treatment with EPB41L3 siRNA upregulated the mRNA and protein expression of N-cadherin. Overexpression of EPB41L3 in MRC5 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of fibronectin and α-SMA. Finally, treatment with EPB41L3 siRNA upregulated the mRNA and protein expression of FN1, COL1A1, and VIM. In conclusion, these data strongly support an inhibitory effect of EPB41L3 on the process of fibrosis and suggest the therapeutic potential of EPB41L3 as an anti-fibrotic mediator.

Uneven codon usage within genes as well as among genomes is a usual phenomenon across organisms. It plays a significant role in the translational efficiency and evolution of a particular gene. EPB41L3 is a tumor suppressor protein-coding gene, and in the present study, the pattern of codon usage was envisaged. The full-length sequences of the EPB41L3 gene for the human, brown rat, domesticated cattle, and Sumatran orangutan available at the NCBI were retrieved and utilized to analyze CUB patterns across the selected mammalian species. Compositional properties, dinucleotide abundance, and parity analysis showed the dominance of A and G whilst RSCU analysis indicated the dominance of G/C-ending codons. The neutrality plot plotted between GC12 and GC3 to determine the variation between the mutation pressure and natural selection indicated the dominance of selection pressure (R = 0.926; p < 0.00001) over the three codon positions across the gene. The result is in concordance with the codon adaptation index analysis and the ENc-GC3 plot analysis, as well as the translational selection index (P2). Overall selection pressure is the dominant pressure acting during the evolution of the EPB41L3 gene.

Erythrocyte membrane protein band 4.1-like 3 (EPB41L3) is an important membrane skeletal protein that may interact with numerous membrane proteins. Loss of EPB41L3 is reported in multiple cancer types, and it is originally identified as a tumor suppressor. In this study, through analyzing expression profiling retrieved from the Gene Expression Omnibus (GEO) dataset, we find that EPB41L3 is upregulated in primary osteosarcoma (OS) and osteosarcoma cell lines. Importantly, EPB41L3 may promote osteosarcoma cell proliferation and suppress osteosarcoma cell migration and invasion. Reduced EPB41L3 leads to a decrease of E-cadherin as well as an increase of N-cadherin and Vimentin, implying a prominent epithelial-to-mesenchymal transition. Furthermore, we demonstrate that EPB41L3 inhibits the epithelial-to-mesenchymal transition through destabilizing the Snai1 protein, one of the most important transcription factors of the epithelial-to-mesenchymal transition process. Collectively, our study has first established the complex and vital roles of EPB41L3 and implicated EPB41L3 as a potential biomarker in osteosarcoma.

UNASSIGNED: The incidence of cervical squamous cell carcinoma (CSCC) has expanded in recent years. However, the function of long non-coding RNA (lncRNA) MAGI2-AS3 in the occurrence and progression of CSCC remains unclear. Therefore, the role of lncRNA MAGI2-AS3 in cervical squamous cell carcinoma (CSCC) was investigated in our study.
UNASSIGNED: We used qRT-PCR analysis to identify the level of MAGI2-AS3 mRNA expression in CSCC clinical samples and cell lines. We investigated cell migration and invasion of CSCC cells transfected with MAGI2-AS3, miR-233 mimic, or EPB41L3 with transwell assays. Bioinformatics analysis and a luciferase reporter assay were employed to predict the interaction between MAGI2-AS3 and miR-233.
UNASSIGNED: We found that MAGI2-AS3 and EPB41L3 were both downregulated in CSCC and the expression of this two was positively correlated. Bioinformatics analysis showed that MAGI2-AS3 might bind to miR-233, which could directly target EPB41L3. In CSCC cells, overexpression of MAGI2-AS3 led to upregulated, while overexpression of miRNA-233 led to downregulated expression of EPB41L3. However, MAGI2-AS3 and miR-233 did not affect the expression of each other. In addition, overexpression of MAGI2-AS3 and EPB41L3 led to inhibited cancer cell invasion and migration, while overexpression of miR-233 played an opposite role and attenuated the effects of overexpressing MAGI2-AS3.
UNASSIGNED: MAGI2-AS3 may sponge miR-233 to upregulate EPB41L3, thereby inhibiting CSCC cell invasion and migration.

暂无摘要。

Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3) is candidate tumor suppressor gene (TSG) in various cancers. EPB41L3 downregulation has been identified in many solid cancers including gastric (GC) and colorectal cancers (CRCs), but somatic inactivating mutation along with protein expression in cancers are largely unexplored. The aim of our study was to find whether EPB41L3 gene was mutated and expressionally altered in GC and CRC. EPB41L3 gene has a mononucleotide repeat in the coding sequence that could be mutated in cancers with high microsatellite instability (MSI-H). We analyzed 79 GCs and 124 CRCs, and found that only one CRC with MSI-H (1.3%) harbored the frameshift mutation within the repeat. In immunohistochemistry, loss of EPB41L3 expression was identified in 49% of GCs and 42% of CRCs. Our data may indicate EPB41L3 that loss of expression but not frameshift mutation may play a role in GC and CRC development by inhibiting TSG functions of EPB41L3.

Gastric cancer is the most common malignant tumor of the digestive system and it is beneficial to find a safer and more effective therapeutic target if we have a deep understanding of the molecular function mechanism during the development of gastric cancer. In recent years, through many researches, we found that miRNA functions as oncogene or cancer suppressor gene, and it plays an important role in the occurrence and development of tumors. Many researches also showed that miR-452 has different expression patterns and roles in different tumors. Its expression is significantly reduced in glioma, breast cancer, colorectal cancer and prostate cancer; however, the expression is significantly increased in liver cancer, renal clear cell carcinoma, esophageal cancer and urothelial carcinoma, etc. However, the role and mechanism of miR-452 in gastric cancer is still unclear. In this study, we found that miR-452 was highly expressed in both tumor tissue and gastric cancer cells, and could directly target the cancer suppressor gene EPB41L3 3\'-UTR. miR-452 significantly promoted the proliferation, migration and the S-phase arrest of gastric cancer cells, but EPB41L3 as a downstream target gene of miR-452 reversed such promoting effect. While down-regulation of miR-452 expression significantly inhibited the malignant biological behavior of gastric cancer cells, but this inhibitory effect was reversed by EPB41L3 siRNA. In addition, miR-452 in the gastric cancer xenograft model in nude mice could down-regulated the expression level of EPB41L3 and promote the growth of transplanted tumor in nude mice. Taken together, this study reveals the role of miR-452 in gastric cancer via inhibiting the target gene EPB41L3, suggesting that miR-452 has the potential to become a new target for the diagnosis and treatment of gastric cancer.

Vigilant management of women with high-risk human papillomavirus (hrHPV) is necessary in cancer screening programs. To this end, we evaluated the performance of S5 (targeting DNA methylation in HPV16, HPV18, HPV31, HPV33, and human gene EPB41L3) to predict cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in a sample of hrHPV-infected women referred to colposcopy in the FRIDA Study, a large screening trial in Mexico. A nested case-control sample with women referred to colposcopy either by atypical squamous cells of undetermined significance or higher (ASCUS+) in cytology and/or positive for HPV types 16 or 18 was tested by S5. Seventy-nine cases of CIN2+ were age-matched to 237 controls without a diagnosis of CIN2+ (The S5 classifier separated women with CIN2+ from S5 testing on hrHPV-positive women significantly increased diagnostic information compared to triage by HPV16/18 plus cytology and appears to have clinical utility as an additional test to substantially lessen burdens on colposcopy.
The FRIDA Study is registered in ClinicalTrials.gov , number NCT02510027.