Association between the expression of epithelial-mesenchymal transition (EMT)-related markers and oncologic outcomes of colorectal cancer.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a key step in the development of colorectal cancer (CRC) that confers metastatic capabilities to cancer cells. The present study aimed to assess the immunohistochemical (IHC) expression and impact of EMT markers, including E-cadherin, Vimentin, ß-catenin, and SMAD4, on the oncologic outcomes of CRC. METHODS: This was a retrospective review of 118 CRC patients. Tissue slides were retrieved from the slide archive and five tissue microarray construction blocks were constructed. IHC for E-cadherin, Vimentin, ß-catenin, and SMAD4 was done. The main outcome was the association between abnormal marker expression and overall survival (OS), and disease-free survival (DFS). RESULTS: Adenocarcinomas accounted for 71.2% of tumors, whereas 25.4% and 3.4% were mucinous and signet ring cell carcinomas. The rates of lymphovascular invasion and perineural invasion were 72.9% and 20.3%, respectively. There was a positive, significant correlation, and association between the four markers. Abnormal expression of E-cadherin was associated with significantly lower OS (p < 0.0001) and similar DFS (p = 0.06). Abnormal Vimentin expression was associated with a significantly higher rate of distant metastasis (p = 0.005) and significantly lower OS and DFS (p < 0.0001). Abnormal expression of ß-catenin was associated with significantly lower OS (p < 0.0001) and similar DFS (p = 0.15). Abnormal expression of SMAD4 was associated with significantly lower OS and DFS (p < 0.0001). Abnormal expression of all four markers was associated with a higher disease recurrence, lower OS, and lower DFS. CONCLUSION: Abnormal expression of each marker was associated with lower OS, whereas abnormal expression of Vimentin and SMAD4 only was associated with lower DFS.

Potential biomarkers: The hypomethylation of cg18949415 and cg22193385 sites in colon adenocarcinoma.

Overall cancer hypomethylation had been identified in the past, but it is not clear exactly which hypomethylation site is the more important for the occurrence of cancer. To identify key hypomethylation sites, we studied the effect of hypomethylation in twelve regions on gene expression in colon adenocarcinoma (COAD). The key DNA methylation sites of cg18949415, cg22193385 and important genes of C6orf223, KRT7 were found by constructing a prognostic model, survival analysis and random combination prediction a series of in-depth systematic calculations and analyses, and the results were validated by GEO database, immune microenvironment, drug and functional enrichment analysis. Based on the expression values of C6orf223, KRT7 genes and the DNA methylation values of cg18949415, cg22193385 sites, the least diversity increment algorithm were used to predict COAD and normal sample. The 100 % reliability and 97.12 % correctness of predicting tumor samples were obtained in jackknife test. Moreover, we found that C6orf223 gene, cg18949415 site play a more important role than KRT7 gene, cg22193385 site in COAD. In addition, we investigate the impact of key methylation sites on three-dimensional chromatin structure. Our results will be help for experimental studies and may be an epigenetic biomarker for COAD.

Involvement of FAM83 Family Proteins in the Development of Solid Tumors: An Update Review.

FAM83 family members are a group of proteins that have been implicated in various solid tumors. In this updated review, we mainly focus on the cellular localization, molecular composition, and biological function of FAM83 family proteins in solid tumors. We discussed the factors that regulate abnormal protein expression and alterations in the functional activities of solid tumor cells (including non-coding microRNAs and protein modifiers) and potential mechanisms of tumorigenesis (including the MAPK, WNT, and TGF-ß signaling pathways). Further, we highlighted the application of FAM83 family proteins in the diagnoses and treatment of different cancers, such as breast, lung, liver, and ovarian cancers from two aspects: molecular marker diagnosis and tumor drug resistance. We described the overexpression of FAM83 genes in various human malignant tumor cells and its relationship with tumor proliferation, migration, invasion, transformation, and drug resistance. Moreover, we explored the prospects and challenges of using tumor treatments based on the FAM83 proteins. Overall, we provide a theoretical basis for harnessing FAM83 family proteins as novel targets in cancer treatment. We believe that this review opens up open new directions for solid tumor treatment in clinical practice.

Mechanisms Controlling MicroRNA Expression in Tumor.

MicroRNAs (miRNAs) are widely present in many organisms and regulate the expression of genes in various biological processes such as cell differentiation, metabolism, and development. Numerous studies have shown that miRNAs are abnormally expressed in tumor tissues and are closely associated with tumorigenesis. MiRNA-based cancer gene therapy has consistently shown promising anti-tumor effects and is recognized as a new field in cancer treatment. So far, some clinical trials involving the treatment of malignancies have been carried out; however, studies of miRNA-based cancer gene therapy are still proceeding slowly. Therefore, furthering our understanding of the regulatory mechanisms of miRNA can bring substantial benefits to the development of miRNA-based gene therapy or other combination therapies and the clinical outcome of patients with cancer. Recent studies have revealed that the aberrant expression of miRNA in tumors is associated with promoter sequence mutation, epigenetic alteration, aberrant RNA modification, etc., showing the complexity of aberrant expression mechanisms of miRNA in tumors. In this paper, we systematically summarized the regulation mechanisms of miRNA expression in tumors, with the aim of providing assistance in the subsequent elucidation of the role of miRNA in tumorigenesis and the development of new strategies for tumor prevention and treatment.

CircRNA: An emerging star in the progression of glioma.

Circular RNAs (circRNAs), a class of single-stranded noncoding RNAs with a covalently closed loop structure, are recognized as promising biomarkers and targets for diagnosing and treating dozens of diseases, especially cancers. CircRNAs are extremely stable, abundant and conserved and have tissue- or developmental stage-specific expression. Currently, the biogenesis and biological functions of circRNAs have been increasingly revealed with deep sequencing and bioinformatics. Studies have indicated that circRNAs are frequently expressed in brain tissues and that their expression levels change in different stages of neural development, suggesting that circRNAs may play an important role in diseases of the nervous system, such as glioma. However, because the biogenesis and functions of circRNAs do not depend on a single mechanism but are coregulated by multiple factors, it is necessary to further explore the underlying mechanisms. In this review, we summarized the classification, mechanisms of biogenesis and biological functions of circRNAs. Meanwhile, we emphatically expounded on the process of abnormal expression of circRNAs, methods used in circRNA research, and their effects on the malignant biological capabilities of glioma.

Differential Expression of Long Noncoding RNAs in Murine Myoblasts After Short Hairpin RNA-Mediated Dysferlin Silencing In Vitro: Microarray Profiling.

BACKGROUND: Long noncoding RNAs (lncRNAs) are noncoding RNA transcripts greater than 200 nucleotides in length and are known to play a role in regulating the transcription of genes involved in vital cellular functions. We hypothesized the disease process in dysferlinopathy is linked to an aberrant expression of lncRNAs and messenger RNAs (mRNAs). OBJECTIVE: In this study, we compared the lncRNA and mRNA expression profiles between wild-type and dysferlin-deficient murine myoblasts (C2C12 cells). METHODS: LncRNA and mRNA expression profiling were performed using a microarray. Several lncRNAs with differential expression were validated using quantitative real-time polymerase chain reaction. Gene Ontology (GO) analysis was performed to understand the functional role of the differentially expressed mRNAs. Further bioinformatics analysis was used to explore the potential function, lncRNA-mRNA correlation, and potential targets of the differentially expressed lncRNAs. RESULTS: We found 3195 lncRNAs and 1966 mRNAs that were differentially expressed. The chromosomal distribution of the differentially expressed lncRNAs and mRNAs was unequal, with chromosome 2 having the highest number of lncRNAs and chromosome 7 having the highest number of mRNAs that were differentially expressed. Pathway analysis of the differentially expressed genes indicated the involvement of several signaling pathways including PI3K-Akt, Hippo, and pathways regulating the pluripotency of stem cells. The differentially expressed genes were also enriched for the GO terms, developmental process and muscle system process. Network analysis identified 8 statistically significant (P<.05) network objects from the upregulated lncRNAs and 3 statistically significant network objects from the downregulated lncRNAs. CONCLUSIONS: Our results thus far imply that dysferlinopathy is associated with an aberrant expression of multiple lncRNAs, many of which may have a specific function in the disease process. GO terms and network analysis suggest a muscle-specific role for these lncRNAs. To elucidate the specific roles of these abnormally expressed noncoding RNAs, further studies engineering their expression are required.

What Has Changed in the Management of Uterine Serous Carcinomas? Two Decades of Experience.

Uterine serous carcinoma accounts for 3-10% of endometrial cancers, but it is the most lethal histopathological subtype. The molecular characterization of endometrial carcinomas has allowed novel therapeutic approaches for these patients. We undertook a retrospective analysis of patients with uterine serous carcinomas treated in our hospital within the last two decades to identify possible changes in their management. The patients and their characteristics were evenly distributed across the two decades. Treatment modalities did not change significantly throughout this period. After adjuvant treatment, patients' median disease-free survival was 42.07 months (95% CI: 20.28-63.85), and it did not differ significantly between the two decades (p = 0.059). The median overall survival was 47.51 months (95% Cl: 32.18-62.83), and it significantly favored the first decade's patients (p = 0.024). In patients with de novo metastatic or recurrent disease, median progression-free survival was 7.8 months (95% Cl: 5.81-9.93), whereas both the median progression-free survival and the median overall survival of these patients did not show any significant improvement during the examined time period. Overall, the results of our study explore the minor changes in respect of uterine serous carcinoma's treatment over the last two decades, which are reflected in the survival outcomes of these patients and consequently underline the critical need for therapeutic advances in the near future.

Perspective of Human Condensins Involved in Colorectal Cancer.

Although many important roles are played by human condesins in condensation and segregation of mitotic chromosomes, what roles of human condensins play in colorectal cancer are still unclear at present. Recently, abnormal expressions of all eight subunits of human condensins have been found in colorectal cancer and they are expected to become potential biomarkers and therapeutic targets for colorectal cancer in the future. However, there are still no reviews on the significance of abnormal expression of human condensin subunits and colorectal cancer until now. Based on a brief introduction to the discovery and composition of human condensins, the review summarized all abnormally expressed human subunits found in colorectal cancer based on publicly published papers. Moreover, Perspective of application on abnormally expressed human subunits in colorectal cancer is further reviewed.

Consequences of Mutations and Abnormal Expression of SMAD4 in Tumors and T Cells.

SMAD4 is a typical tumor suppressor in the TGF-ß signaling pathway. In human cancers, SMAD4 is frequently mutated and inactivated. In recent years, the consequences of mutations and inactivation of SMAD4 are gradually becoming clearer. Most of the mutations have negative consequences and reduce the chances of survival of their carriers. Loss of SMAD4 functions due to mutations or abnormal expression can suppress the inhibition of tumor growth and support the tumor progression. Functions of SMAD4 and its variants in T cells are being studied extensively, to better understand the SMAD4 functions in T cells. In this review, we mainly discuss the recently reported consequences of mutations and abnormal expression of SMAD4 in tumors, and the effects of loss, deficiency or mutation of SMAD4 and its T cells, to show the use of SMAD4 mutations in cancer diagnosis and therapeutic strategies.

The role of the fibroblast growth factor family in bone-related diseases.

Fibroblast growth factor (FGF) family members are important regulators of cell growth, proliferation, differentiation, and regeneration. The abnormal expression of certain FGF family members can cause skeletal diseases, including achondroplasia, craniosynostosis syndrome, osteoarthritis, and Kashin-Beck disease. Accumulating evidence shows that FGFs play a crucial role in the growth and proliferation of bone and in the pathogenesis of certain bone-related diseases. Here, we review the involvement of FGFs in bone-related processes and diseases; FGF1 in the differentiation of human bone marrow mesenchymal stem cells and fracture repair; FGF2, FGF9, and FGF18 in osteoarthritis; FGF6 in bone and muscle injury; FGF8 in osteoarthritis and Kashin-Beck disease; and FGF21 and FGF23 on bone regulation. These findings indicate that FGFs are targets for novel therapeutic interventions for bone-related diseases.

Gene and microRNA Signatures Are Associated with the Development and Survival of Glioblastoma Patients.

This study was aimed to identify hub genes associated with the development of glioblastoma (GBM) by conducting a bioinformatic analysis. The raw gene expression data were downloaded from the Gene Expression Omnibus database and The Cancer Genome Atlas project. After the differentially expressed genes (DEGs) were identified, the functional enrichment analysis of DEGs was conducted. Subsequently, the protein-protein interaction (PPI) network, molecular complex detection clusters, and transcriptional factor (TF)-miRNA-target regulatory network were constructed, respectively. Furthermore, the survival analysis of prognostic outcomes and genes was analyzed. In addition, the expression of key genes was validated by quantitative real-time PCR (qRT-PCR) analysis. A total of 884 DEGs, including 418 upregulated and downregulated genes, were identified between GBM and normal samples. The PPI network comprised a set of 3418 pairs involving 751 nodes, and AKT1 and CDK2 were the critical genes in the network. A total of seven clusters were identified, the genes in which were intensively associated with cell cycle, cholinergic synapse, and extracellular matrix (ECM)-receptor interaction. qRT-PCR analysis indicated that AKT1 and CDK2 were significantly upregulated, and NRXN3 and NPTX2 were significantly downregulated in GBM samples. The TF-miRNA-target regulatory networks were built, in which CCNB1, RFC5, microRNA524, and microRNA34b were key regulators. There were 43 genes, including NPTX2 and NRXN3, significantly related to the prognostic outcomes of GBM patients. These crucial genes might be promising options for GBM treatment.

Effects of miR-181a-5p abnormal expression on zebrafish (Danio rerio) vascular development following triclosan exposure.

Triclosan (TCS), one of the important bactericides, is widely used in personal care products, and its chronic exposure leads to severe toxic effects on the growth and development of blood vessels in zebrafish (Danio rerio). Herein, we screened out three differentially expressed miRNAs (miR-181a-5p, miR-132-3p and miR-128-3p) by sequencing and qRT-PCR analyses of 4-96-hpf TCS-exposed zebrafish, among which miR-181a-5p was found to regulate many signaling pathways involved in fatty acid biosynthesis and phosphatidylimositol signaling systems. By O-dianisidine staining, TCS-exposure resulted in decreased distribution of red blood cells and induced blood hypercoagulable state and thrombotic effects. Defective subintestinal veins (SIVs), and decreased branching and curvature of blood vessels were observed with increasing TCS-exposure concentrations. After microinjection of miR-181a-5p mimic and inhibitor, zebrafish malformation type and percentage were prominently increased such as distorted SIV vessels along with reduced venation and abnormal branches by ALP staining. Overexpressed miR-181a-5p had a greater effect on development and branching patterns of arteries and veins than its knockdown. By laser confocal microscopy observation, the 72-hpf Tg (flk1: mCherry) zebrafish obviously displayed vascular proliferation and ablation in the miR-181a-5p mimic group. Microinjection of miR-181a-5p mimics and inhibitors led to abnormal expressions (20-50%) of two key target genes (pax2a and vash2) by WISH, and increased malformation percentages (18-45%) by IOD analysis. Overexpression of vash2 led to the inhibitory or promoting effects on the expression of PI3K signaling pathway-related genes, proving that the effect of vash2 on development of blood vessels could be realized by inhibiting PI3K signaling pathway. These observations lay theoretical foundation for deep insight into the molecular mechanisms on TCS-induced cardiovascular diseases.

[The research progress of CPEB4 in tumor].

Cytoplasmic polyadenylation element binding protein 4 (Cytoplasmic polyadenylation element binding protein 4, CPEB4) ,a newly discovered member of the cytoplasmic polyadenylation element binding proteins, is a kind of RNA binding proteins with mediator of mRNA cytoplasmic polyadenylation and translation. CPEB4 plays an important role in the proliferation, migration, invasion and interstitial transformation of many tumors. In recent years, studies have shown that CPEB4 has abnormal expression in a variety of human tumors, and the abnormal expression of cancer patients has a significant correlation with the prognosis. Based on the current research progress, the purpose of this article is to further understand the relationship between CPEB4 and malignant tumor and its molecular mechanism of regulating tumorigenesis and to provide a new direction and means for the molecular diagnosis and targeted therapy of malignant tumor.

Research progress of microRNA-214 in the cervical cancer / 医学研究生学报

MicroRNAs ( miRNAs ) play important roles in the processes of the occurrence and development of cancers , through regulating tumor related gene expression at post-transcription.It has shown that the expression of miR-214 is aberrant in cervi-cal cancer.Also,miR-214 could affect the proliferation, migration, invasion and apoptosis of tumor cells by targeting various genes . This article focuses on the studies of miR-214 function in cervical cancer , and will provide a novel approach for the clinical diagnosis and the treatment of cervical cancer .

Research progress of a new oncotherapy target TRAP1 / 中国药理学通报

Tumor necrosis factor receptor-associated protein 1 (TRAP1),as one of the main members of the heat shock protein 90 family, resists oxidative stress-induced apoptosis as well as predominantly maintains the integrity of mitochondria and cellu-lar homeostasis. Abnormal expression of TRAP1 was herein closely related to the onset and progression of a wide variety of tumors. As a key regulatory factor mediating energy metabolism within tumor cells, TRAP1 may be able to kill them by interfer-ing with such metabolism. More importantly, the abnormal ex-pression of TRAP1 played a less important role in normal cells, allowing TRAP1 to be a particularly attractive target as it can be used in tumor treatment or interference. The relationship be-tween abnormal expression of TRAP1 protein and tumor onset was reviewed. Besides, the mechanism by which disordered TRAP1 protein expression induced tumor formation was postula-ted, which may provide references for future research and clini-cal treatment.

The research progression on the relationship between TRPS1 and tumors / 实用肿瘤学杂志

Tricho-rhinophalangeal syndrome -1 gene(TRPS1),a new GATA family member,is highly prevalent in many tissues .It plays an important role in the regulation of cell proliferation and tissue development . The genetic missing of TRPS1 may lead to Tricho-rhinophalangeal syndrome .In recent years,studies have dem-onstrated that TRPS1 abnormal expression exists in a variety of tumors , and is associated with carcinogenesis , lymph node metastasis,pathological grading and clinical staging .Therefore,TRPS1 is considered as a potential tumor suppressor gene ,its overexpression may be one of mechanisms for carcinogenesis and progression of cancer . This review focuses on the role of TRPS 1 gene in carcinogenesis and progression of carcinoma ,and further to pro-vide a new biomarker for predicting cancer prognosis and therapy .

Advances on abnormal expression of E-cadherin with bronchial asthma / 中国药理学通报

Bronchial asthma is a kind of respiratory disease which affects people 's life quality seriously. Many factors in-volved in the occurrence and development of such disease, of which the aberrant expression of E-cad plays a critical role in it. Research found that E-cad is an important cell adhesion molecu-lar, and its main function is to maintain the structural integrity of cells and participate in the improvement of airway remodeling as well as restoration of immune function. Further study showed that the role of mucosal barrier of airway epithelial cells in bronchial asthma patients was often damaged. Moreover, the protein ex-pression of E-cad decreased significantly in mucosal molecular, which suggested that the abnormal expression of E-cad was in-volved in the development of bronchial asthma. A review on the relations between the abnormal expression of E-cad protein and bronchial asthma has been discussed in this paper, also it in-cludes the discussion about the mechanisms of E-cad’ s disorder-induced bronchial asthma as well as explores the strategies of bronchial asthma treatment, which may provide references for the follow-up research and clinical treatment.

Research progress on ion channels in human glioma / 肿瘤研究与临床

Glioma is a serious threat to human health.Increasing evidences indicate that abnormal expression and activities of a number of ion channels,e.g.voltage-gated K+,Ca2+,C1-channels,are involved in the growth,proliferation,migration and invasion of glioma cells.Ion channels may affect the occurrence and development of glioma cells through regulating the membrane potential,adjusting the cytoplasmic volume,ion concentration,and pH value.In-depth understanding the role of ion channels in formation,development and transfer process of glioma may provide new targets for glioma prevention and treatment.In this paper,the advanced studies of ion channels in glioma were briefly reviewed.

The relationship between EphB receptor and the development of tumor / 实用肿瘤学杂志

Currently ,EphB receptor has been demonstrated as an important factor on the biological be -havior of normal cells .Some studies found that it plays an important role in the regulation of normal cell morpholo -gy,cell adhesion ,migration and angiogenesis .There is a certain relationship between abnormal expression of EphB receptor with a variety of tumor development .Visiblely,EphB receptor is important research direction in cancer studies,understanding the relationship between EphB receptor and tumor can better realize the progress of the tumor,and further to provide more scientific basis for cancer treatment and prevention .

Advances on LKB1 in the study of lung cancer / 中国癌症杂志

Recent studies have shown that the loss-of-function LKB1 mutations occur in approximately 30% of human non-small cell lung cancer(NSCLC). Studies from lung cancer animal models have demonstrated that functional loss of LKB1 dramatically promotes lung cancer invasion and progression, underscoring the essential role of LKB1 as a potent tumor suppressor involved in lung cancerigenesis, differentiation and metastasis. However, the relationship between loss-of-function LKB1 mutations and lung cancer prognosis remain largely unclear, therefore, we summarized the progress of the research on LKB1.