SYVN1 modulates papillary thyroid carcinoma progression by destabilizing HMGB1.

E3 ubiquitin ligase synoviolin (SYVN1) has been reported to participate in many human cancers. This study aimed to investigate SYVN1's roles and molecular pathways in papillary thyroid cancer (PTC). The functions of SYVN1 in PTC were further analyzed using gain- and loss-of-function methods and numerous investigations in cellular function and molecular biology. The findings demonstrated that the overexpression of SYVN1 markedly suppressed the proliferation, migration, and invasion of PTC cell lines (NPA87 and TPC-1). We found that SYVN1 interacted with HMGB1 and promoted its ubiquitination and degradation. In addition, SYVN1 effectively impairs cell proliferation, migration, invasion, and the formation of tumor xenografts in mice models. However, this effect may be partly reversed by overexpressing HMGB1. Thus, SYVN1 may inhibit the proliferation, migration, and invasion of PTC cells by disrupting HMGB1. Consequently, SYVN1 might be considered a promising therapeutic target for PTC.

Direct control of shell regeneration by the mantle tissue in the pearl oyster Pinctada fucata.

Molluscs rapidly repair the damaged shells to prevent further injury, which is vital for their survival after physical or biological aggression. However, it remains unclear how this process is precisely controlled. In this study, we applied scanning electronic microscope and histochemical analysis to examine the detailed shell regeneration process in the pearl oyster Pinctada fucata. It was found that the shell damage caused the mantle tissue to retract, which resulted in relocation of the partitioned mantle zones with respect to their correspondingly secreting shell layers. As a result, the relocated mantle tissue dramatically altered the shell morphology by initiating de novo precipitation of prismatic layers on the former nacreous layers, leading to the formation of sandwich-like "prism-nacre-prism-nacre" structure. Real-time PCR revealed the up-regulation of the shell matrix protein genes, which was confirmed by the thermal gravimetric analysis of the newly formed shell. The increased matrix secretion might have led to the change of CaCO3 precipitation dynamics which altered the mineral morphology and promoted shell formation. Taken together, our study revealed the close relationship between the physiological activities of the mantle tissue and the morphological change of the regenerated shells.

Mantle tissue in the pearl oyster Pinctada fucata secretes immune components via vesicle transportation.

Molluscan bivalves secrete shell matrices into the extrapallial space (EPS) to guide the precipitation of rigid shells. Meanwhile, immune components are present in the EPS and shell matrices, which are pivotal in resistant to invaded pathogens, thus ensuring the shell formation process. However, the origin of these components remains unclear. In this study, we revealed numerous vesicles were secreted from the outer mantle epithelial cells by using light and electron microscopes. The secreted vesicles were isolated by gradient centrifugation and confirmed by transmission electron microscopy. Proteomics analysis showed that the secreted vesicles were composed of cytoplasmic and immune components, most of which do not have signal peptides, indicating that they were secreted by a non-classical pathway. Moreover, real-time PCR revealed that some immune components were highly expressed in the mantle tissue, compared to the hemocytes. FTIR analysis verified the presence of lipids in the shell matrices, indicating that the vesicles have integrated into the shell layers. Taken together, our results suggested that mantle epithelial cells secreted some important immune components into the EPS via secreted vesicle transportation, thus cooperating with the hemocytes to play a vital role in immunity during shell formation.

Microplastics impact shell and pearl biomineralization of the pearl oyster Pinctada fucata.

Microplastics are extremely widespread aquatic pollutants that severely detriment marine life. In this study, the influence of microplastics on biomineralization was investigated. For the first time, multiple forms and types of microplastics were detected and isolated from the shells and pearls of Pinctada fucata. According to the present study, the abundance of microplastics in shells and pearls was estimated at 1.95 ± 1.43 items/g and 0.53 ± 0.37 items/g respectively. Interestingly, microplastics were less abundant in high-quality round pearls. Microplastics may hinder the growth of calcite and aragonite crystals, which are crucial components required for shell formation. During the process of biomineralization microplastics became embedded in shells, suggesting the existence of a novel pathway by which microplastics accumulate in bivalves. After a 96-h exposure to microplastics, the expression level of typical biomineralization-related genes increased, including amorphous calcium carbonate binding protein (ACCBP) gene which experienced a significant increase. ACCBP promotes the formation of amorphous calcium carbonate (ACC), which is the pivotal precursor of shell formation-related biominerals. ACCBP is highly expressed during the developmental stage of juvenile oysters and the shell-damage repair process. The increased expression of ACCBP suggests biomineralization is enhanced as a result of microplastics exposure. These results provide important evidence that microplastics exposure may impact the appearance of biominerals and the expression of biomineralization-related genes, posing a new potential threat to aquatic organisms.

Transition from horizontal expansion to vertical growth in the oyster prismatic layer.

Biomimetic materials inspired by biominerals have substantial applications in various fields. The prismatic layer of bivalve molluscs has extraordinary flexibility compared to inorganic CaCO3. Previous studies showed that in the early stage, minerals expanded horizontally and formed prism domains as a Voronoi division, while the evolution of the mature prisms were thermodynamically driven, which was similar to grain growth. However, it was unclear how the two processes were correlated during shell formation. In this study, we used scanning electronic microscopy and laser confocal scanning microscopy to look into the microstructure of the columnar prismatic layer in the pearl oyster Pinctada fucata. The Dirichlet centers of the growing domains in mature prisms were calculated, and the corresponding Voronoi division was reconstructed. It was found that the domain pattern did not fit the Voronoi division, indicating the driving forces of the mature prisms evolution and the initiation stage were different. During the transition from horizontal expansion to vertical growth, the minerals broke through the inner periostracum and squeezed out the organic materials to the inter-prism space. Re-arrangement of the organic framework pattern was driven by elastic relaxation at the vertices, indicating the transition process was thermodynamically driven. Our study provided insights into shell growth in bivalves and pave the way to synthesize three-dimensional material biomimetically.

Identification of lncRNA MEG3 Binding Protein Using MS2-Tagged RNA Affinity Purification and Mass Spectrometry.

Long noncoding RNAs (lncRNAs) are nonprotein coding transcripts longer than 200 nucleotides. Recently in mammals, thousands of long noncoding RNAs have been identified and studied as key molecular players in different biological processes with protein complexes. As a long noncoding RNA, maternally expressed gene 3 (MEG3) plays an important role in many cellular processes. However, the mechanism underlying MEG3 regulatory effects remains enigmatic. By using the specific interaction between MS2 coat protein and MS2 RNA hairpin, we developed a method (MS2-tagged RNA affinity purification and mass spectrometry (MTRAP-MS)) to identify proteins that interact with MEG3. Mass spectrometry and gene ontology (GO) analysis showed that MEG3 binding proteins possess nucleotide binding properties and take part in transport, translation, and other biological processes. In addition, interleukin enhancer binding factor 3 (ILF3) and poly(A) binding protein, cytoplasmic 3 (PABPC3) were validated for their interaction with MEG3. These findings indicate that the newly developed method can effectively enrich lncRNA binding proteins and provides a strong basis for studying MEG3 functions.

MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: microRNAs (miRNAs), small non-coding RNAs, are always aberrantly expressed in many diseases including human cancers. The aim of this study was to examine and determine the clinical significance of hsa-miR-31, hsa-miR-142-3p, hsa-miR-338-3p, and hsa-miR-1261 expression in esophageal squamous cell carcinoma (ESCC). METHODS: Expression levels of four selected miRNAs, initially evaluated by microarray, were validated by qRT-PCR. Various statistical methods were used to analyze the relationship between miRNA expression and clinicopathologic features and prognosis in 91 patients with ESCC. RESULTS: MiR-31 and miR-142-3p expression were correlated to histological differentiation in ESCC (P < 0.05, Student's t-test); high miR-142-3p expression was associated with a poor prognosis in all 91 ESCC patients (P = 0.014, log-rank) and identified as an independent prognostic factor in ESCC (P = 0.017, univariate Cox; P = 0.022, multivariate Cox). More importantly, stratified analysis indicated that high miR-142-3p expression was correlated to a poor prognosis within good-prognosis groups comprised of ESCC patients with small tumor size, negative lymph node metastasis, or early stage (all P < 0.05). CONCLUSION: The main findings suggest that miR-142-3p is involved in the progression of ESCC and is a potential prognostic biomarker for ESCC.