Implications of TDP-43 in non-neuronal systems

Abstract TAR DNA-binding protein 43 (TDP-43) is a versatile RNA/DNA-binding protein with multifaceted processes. While TDP-43 has been extensively studied in the context of degenerative diseases, recent evidence has also highlighted its crucial involvement in diverse life processes beyond neurodegeneration. Here, we mainly reviewed the function of TDP-43 in non-neurodegenerative physiological and pathological processes, including spermatogenesis, embryonic development, mammary gland development, tumor formation, and viral infection, highlighting its importance as a key regulatory factor for the maintenance of normal functions throughout life. TDP-43 exhibits diverse and sometimes opposite functionality across different cell types through various mechanisms, and its roles can shift at distinct stages within the same biological system. Consequently, TDP-43 operates in both a context-dependent and a stage-specific manner in response to a variety of internal and external stimuli. Video Abstrac

Hsa_circ_0046264 up-regulated BRCA2 to suppress lung cancer through targeting hsa-miR-1245

Abstract Objective Lung cancer had been leading mounts of deaths worldwide. Advances in genes microarray had helped human further understand genes and identify novel circular RNAs. This study aimed at investigating the biological functions and molecular mechanisms of hsa_circ_0046264 in lung cancer which may be helpful in lung cancer early diagnosis and clinical treatment. Methods Gene microarray data screened the differential gene of hsa_circ_0046264 and its downstream genes were found by bioinformatics analysis and verified by luciferase reporter assay. QRT-PCR and Western blot was used to detect the RNA and protein levels respectively. RNase R digestion confirmed the existences of circular RNA. Cell viability, invasion and apoptosis were determined by MTT assay, flow cytometry and DNA damage assay. Tumor formation in nude mice and immunohistochemistry proved the functions of hsa_circ_0046264 in vivo. Results Hsa_circ_0046264 and BRCA2 were down-regulated in lung cancer tissues while miR-1245 was up-regulated. Hsa_circ_0046264 induced apoptosis but inhibited proliferation and invasion of lung cancer cells through targeting miR-1245 to up-regulate BRCA2. Hsa_circ_0046264 inhibited the tumor growth in vivo. Conclusion Hsa_circ_0046264 was a tumor suppressor in lung cancer. Overexpression of hsa_circ_0046264 could up-regulate BRCA2 expression through down-regulating of miR-1245

The co-existence of two growth hormone receptors in teleost fish and their differential signal transduction, tissue distribution and hormonal regulation of expression in seabream

Two genomic contigs of putative growth hormone receptors (GHRs) were identified in fugu and zebrafish genomes by in silico analysis, suggesting the presence of two GHR subtypes in a single teleost species. We have tested this hypothesis by cloning the full-length cDNA sequence of a second GHR subtype from the black seabream in which the first GHR subtype had been previously reported by us. In addition, we had also cloned the sequences of both GHR subtypes from two other fish species, namely the Southern catfish and the Nile tilapia. Phylogenetic analysis of known GHR sequences from various vertebrates revealed that fish GHRs cluster into two distinct clades, viz. GHR1 and GHR2. One clade (GHR1), containing 6 to 7 extracellular cysteine residues, is structurally more akin to the non-teleost GHRs. The other clade (GHR2), containing only 4 to 5 extracellular cysteine residues, is unique to teleosts and is structurally more divergent from the non-teleost GHRs. In addition, we had examined the biological activities of both GHR subtypes from seabream using a number of reporter transcription assays in cultured eukaryotic cells and demonstrated that both of them were able to activate the Spi 2.1 and β-casein promoters upon receptor stimulation in a ligand specific manner. In contrast, only GHR1 but not GHR2 in seabream could trigger the c-fos promoter activity, indicating that the two GHR subtypes possess some differences in their signal transduction mechanisms. Also, the expression of GHR2 is significantly higher than GHR1 in many tissues of the seabream including the gonad, kidney, muscle, pituitary and spleen. In vivo hormone treatment data indicated that cortisol upregulated hepatic GHR1 expression in seabream but not GHR2, whereas testosterone decreased hepatic GHR2 expression but not GHR1. On the other hand, hepatic expression of both GHR1 and GHR2 in seabream was decreased by estradiol treatment. © 2006 Society for Endocrinology.Link_to_subscribed_fulltex

Soil C:N:P Stoichiometry Succession and Land Use Effect after Intensive Reclamation: A Case Study on the Yangtze River Floodplain

The coupling cycles of soil carbon (C), nitrogen (N), and phosphorus (P) have a significant impact on biogeochemical processes and ecosystem services. For centuries, large areas of floodplain wetlands in China have been extensively reclaimed for agricultural purposes due to population growth. However, little is known about the evolution of soil C:N:P stoichiometry along a reclamation chronosequence, particularly across different land uses. In this study, we investigated the variations in soil C:N:P ratios with land use and time gradients along a reclamation chronosequence comprising c. 0, 60, 100, 280, 2000, and 3000 years. Land reclamation induced nutrient decoupling, as it facilitated C and N accumulation from biological processes but restricted P supply controlled by geochemical processes. Soil C and N sequestration reached a stable state after 2000 years, while P declined steadily from 60 years. Soil C/P and N/P increased significantly and were controlled by organic carbon (OC) and total nitrogen (TN), respectively, indicating that an increase in C and N could also promote P uptake. Soil C/N declined in the first 60 years and stabilized at a threshold of 10:1. Different land use patterns following reclamation resulted in distinct soil nutrient structures. Paddies retained more OC and TN but exhibited lower adsorption of total phosphorus (TP) compared to adjacent dryland, leading to significant differences in C/P and N/P between land uses. Based on the redundancy analysis and random forest model, soil OC and TN were mainly affected by the abundance of bacteria metabolizing cellulose, while metal oxides, including Fe2O3 and CaO, could best predict TP. Soil C/P and N/P were mainly driven by soil texture and rose significantly with the increasing proportion of clay particles. Our study suggests that as reclamation proceeds, more anthropogenic management is required to regulate potential nutrient imbalances in order to prevent adverse effects on crop growth, soil quality, and ecosystem health. Additionally, any fertilization strategy should be developed based on dryland C and N deficiencies, and lack of P in paddies

NEAT1 is Required for Survival of Breast Cancer Cells Through FUS and miR-548

Increasing evidence shows that long noncoding RNAs (lncRNAs) have important roles in the regulation of multiple cellular processes, including cell division, cell growth, and apoptosis, as well as cancer metastasis and neurological disease progression; however, the mechanism of how lncRNAs regulate these processes is not well established. In this study, we demonstrated that downregulating the expression of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in breast cancer cells inhibited cell growth and induced cell apoptosis. In addition, the RNA-binding protein fused in sarcoma/translocated in liposarcoma (FUS/TLS) physically interacted with NEAT1, and reducing the expression of FUS/TLS also induced cell apoptosis. Multiple miRNAs were identified as regulators of NEAT1, but only overexpression of miR-548ar was able to decrease NEAT1 expression and promote apoptosis. These results indicate a novel interaction between NEAT1, miR-548ar-3p, and FUS and their role in the regulation of breast cancer cell apoptosis

Changes in the mammary gland during aging and its links with breast diseases

The functional capacity of organisms declines in the process of aging. In the case of breast tissue, abnormal mammary gland development can lead to dysfunction in milk secretion, a primary function, as well as the onset of various diseases, such as breast cancer. In the process of aging, the terminal duct lobular units (TDLUs) within the breast undergo gradual degeneration, while the proportion of adipose tissue in the breast continues to increase and hormonal levels in the breast change accordingly. Here, we review changes in morphology, internal structure, and cellular composition that occur in the mammary gland during aging. We also explore the emerging mechanisms of breast aging and the relationship between changes during aging and breast-related diseases, as well as potential interventions for delaying mammary gland aging and preventing breast disease

NEAT1 is Required for Survival of Breast Cancer Cells through FUS and miR-548

Increasing evidence shows that long noncoding RNAs (lncRNAs) have important roles in the regulation of multiple cellular processes, including cell division, cell growth, and apoptosis, as well as cancer metastasis and neurological disease progression; however, the mechanism of how lncRNAs regulate these processes is not well established. In this study, we demonstrated that downregulating the expression of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in breast cancer cells inhibited cell growth and induced cell apoptosis. In addition, the RNA-binding protein fused in sarcoma/translocated in liposarcoma (FUS/TLS) physically interacted with NEAT1, and reducing the expression of FUS/TLS also induced cell apoptosis. Multiple miRNAs were identified as regulators of NEAT1, but only overexpression of miR-548ar was able to decrease NEAT1 expression and promote apoptosis. These results indicate a novel interaction between NEAT1, miR-548ar-3p, and FUS and their role in the regulation of breast cancer cell apoptosis

Additional file 1: of Hsa_circ_0046264 up-regulated BRCA2 to suppress lung cancer through targeting hsa-miR-1245

Figure S1. Hsa_circ_0046264 overexpression promoted DNA damage in vitro. (A) The expression of Îł-H2AX in circ264 group was significantly higher than in control group in A549 cells. (B) The expression of Îł-H2AX in circ264 group was significantly higher than in control group in 95-D cells (TIF 9699 kb)

Functional activity of RLIM/Rnf12 is regulated by phosphorylation-dependent nucleo-cytoplasmic shuttling

The X-linked gene Rnf12 encodes the ubiquitin ligase RLIM/Rnf12 which serves as a major sex-specific epigenetic regulator of female mouse nurturing tissues. Early during embryogenesis, RLIM/Rnf12 expressed from the maternal allele is crucial for the development of extraembryonic trophoblast cells. In contrast, in mammary glands of pregnant and lactating adult females RLIM/Rnf12 expressed from the paternal allele functions as a critical survival factor for milk producing alveolar cells. While RLIM/Rnf12 is detected mostly in the nucleus, little is known about how and in which cellular compartment(s) RLIM/Rnf12 mediates its biological functions. Here, we demonstrate that RLIM/Rnf12 protein shuttles between the nucleus and cytoplasm and that this is regulated by phosphorylation of serine S214 located within its nuclear localization sequence (NLS). We show that shuttling is important for RLIM to exert its biological functions, as alveolar cell survival activity is inhibited in shuttling-deficient nuclear or cytoplasmic RLIM/Rnf12. Thus, the regulated nucleo-cytoplasmic shuttling of RLIM/Rnf12 coordinates cellular compartments during alveolar cell survival