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.

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, β-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, β-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 β-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.
CONCLUSIONS: Abnormal expression of each marker was associated with lower OS, whereas abnormal expression of Vimentin and SMAD4 only was associated with lower DFS.

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-β 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.

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.

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.

SMAD4 is a typical tumor suppressor in the TGF-β 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.

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.

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.