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Some rare earth elements are occupational and environmental toxicants and can cause organ and systemic damage; therefore, they have attracted global attention. Neodymium oxide (Nd2O3) is a rare earth element that is refined and significantly utilized in China. The long noncoding RNA (lncRNA) H19 is encoded by the H19/IGF2 imprinted gene cluster located on human chromosome 11p15.5. H19 has become a research focus due to its ectopic expression leading to the promotion of fibrosis. However, the mechanisms by which it causes pulmonary fibrosis are elusive. This investigation indicates that biologically active Nd2O3 increases H19, SNIP1, and c-myc, decreases miR-29a-3p, accelerates macrophage M2 polarization, and causes pulmonary fibrosis in mice lung tissues. In macrophage-differentiated THP-1 cells, Nd2O3 (25 μg/ml) enhanced H19, SNIP1, and c-myc, reduced miR-29a-3p, accelerated macrophages M2 polarization, and stimulated fibrogenic cytokine (TGF-β1) secretion. Furthermore, the coculturing of Nd2O3-treated macrophage-differentiated THP-1 cells. And human embryonic lung fibroblast cells activated lung fibroblast, which increases the levels of collagen I, α-SMA, p-Smad2/3, and Smad4, whereas H19 knockdown or miR-29a-3p upregulation in macrophages had opposite effects. Moreover, it was revealed that H19/miR-29a-3p/SNIP1/c-myc regulatory axis is involved in pulmonary fibrosis induced by Nd2O3. Therefore, this study provides new molecular insights into the mechanism of pulmonary fibrosis by Nd2O3. [ABSTRACT FROM AUTHOR]

Some rare earth elements are occupational and environmental toxicants and can cause organ and systemic damage; therefore, they have attracted global attention. Neodymium oxide (Nd2O3) is a rare earth element that is refined and significantly utilized in China. The long noncoding RNA (lncRNA) H19 is encoded by the H19/IGF2 imprinted gene cluster located on human chromosome 11p15.5. H19 has become a research focus due to its ectopic expression leading to the promotion of fibrosis. However, the mechanisms by which it causes pulmonary fibrosis are elusive. This investigation indicates that biologically active Nd2O3 increases H19, SNIP1, and c-myc, decreases miR-29a-3p, accelerates macrophage M2 polarization, and causes pulmonary fibrosis in mice lung tissues. In macrophage-differentiated THP-1 cells, Nd2O3 (25 μg/ml) enhanced H19, SNIP1, and c-myc, reduced miR-29a-3p, accelerated macrophages M2 polarization, and stimulated fibrogenic cytokine (TGF-β1) secretion. Furthermore, the coculturing of Nd2O3-treated macrophage-differentiated THP-1 cells. And human embryonic lung fibroblast cells activated lung fibroblast, which increases the levels of collagen I, α-SMA, p-Smad2/3, and Smad4, whereas H19 knockdown or miR-29a-3p upregulation in macrophages had opposite effects. Moreover, it was revealed that H19/miR-29a-3p/SNIP1/c-myc regulatory axis is involved in pulmonary fibrosis induced by Nd2O3. Therefore, this study provides new molecular insights into the mechanism of pulmonary fibrosis by Nd2O3. [ABSTRACT FROM AUTHOR]

Abstract Background The Makorin ring finger protein 1 (MKRN1) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of MKRN1 in colorectal cancer (CRC) development. Methods MKRN1 expression in CRC was analysed using the Cancer Cell Line Encyclopaedia and the Cancer Genome Atlas (TCGA) databases. Rectal tumour tissues were frozen to explore the MKRN1 expression in CRC and its clinical significance. The impact of MKRN1 on CRC cell proliferation and migration was observed using CCK8, colony formation, wound healing, and transwell assays. A combination of MKRN1 quantitative proteomics, ubiquitination modification omics analysis, and a string of in vitro and in vivo experiments revealed the potential mechanisms by which MKRN1 regulates CRC metastasis. Results MKRN1 expression was significantly elevated in CRC tissues compared to paracancerous tissues and was positively linked with prognosis (P

Smad intranuclear binding protein 1 (SNIP1), a highly conserved nuclear protein, functions as a transcriptional regulator and exerts a significant influence on disease progression. In addition, the N-terminal domain of SNIP1 facilitates its interaction with Smad4, a signaling protein associated with the TGF-β family, and RelA/p65, a transcription factor connected to NF-κB. This interaction further enhances the transcriptional activation of c-Myc-dependent genes. Presently, the primary emphasis in research is directed towards targeting the catalytic domain of SNIP1, as it holds promise as a potential therapeutic target for various diseases. While the significance of SNIP1 in pathological mechanisms remains uncertain, this review aims to comprehensively examine the existing literature on the association between SNIP1 and proteins implicated in the regulation of diverse clinical conditions, including cancer, inflammation, and related diseases.

Background: The Makorin ring finger protein 1 (MKRN1) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of MKRN1 in colorectal cancer (CRC) development. Methods: MKRN1 expression in CRC was analysed using the Cancer Cell Line Encyclopaedia and the Cancer Genome Atlas (TCGA) databases. Rectal tumour tissues were frozen to explore the MKRN1 expression in CRC and its clinical significance. The impact of MKRN1 on CRC cell proliferation and migration was observed using CCK8, colony formation, wound healing, and transwell assays. A combination of MKRN1 quantitative proteomics, ubiquitination modification omics analysis, and a string of in vitro and in vivo experiments revealed the potential mechanisms by which MKRN1 regulates CRC metastasis. Results: MKRN1 expression was significantly elevated in CRC tissues compared to paracancerous tissues and was positively linked with prognosis (P < 0.01). MKRN1 downregulation inhibits CRC cell proliferation, migration, and invasion. Conversely, MKRN1 overexpression promotes the proliferation, migration, and invasion of CRC cells. Mechanistically, MKRN1 induces epithelial-mesenchymal transition (EMT) in CRC cells via ubiquitination and degradation of Smad nuclear-interacting protein 1 (SNIP1). Furthermore, SNIP1 inhibits transforming growth factor-β (TGF-β) signalling, and MKRN1 promotes TGF-β signalling by degrading SNIP1 to induce EMT in CRC cells. Finally, using conditional knockout mice, intestinal lesions and metastatic liver microlesions were greatly reduced in the intestinal knockout MKRN1 group compared to that in the control group. Conclusions: High MKRN1 levels promote TGF-β signalling through ubiquitination and degradation of SNIP1, thereby facilitating CRC metastasis, and supporting MKRN1 as a CRC pro-cancer factor. The MKRN1/SNIP1/TGF-β axis may be a potential therapeutic target in CRC. [ABSTRACT FROM AUTHOR]

Abstract Background MicroRNAs (miRNAs) play crucial roles in the development of various cancers. Here, we aimed to evaluate the roles of miR‐138‐5p in lung cancer progression and the value of miR‐138‐5p in lung cancer diagnosis. Methods Quantitative real‐time PCR was performed to examine the expressions of miR‐138‐5p and smad nuclear interacting protein 1 (SNIP1) mRNA. The diagnostic value of miR‐138‐5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. We explored the effect of miR‐138‐5p on cell proliferation and metastasis by CCK‐8, colony formation, wound healing and transwell assays. Western blot was employed to detect the protein expression of SNIP1 and related genes. Lung cancer cell growth was evaluated in vivo using xenograft tumor assay. Results MiR‐138‐5p was decreased in the serum of patients with non‐small cell lung cancer (NSCLC) and in NSCLC cells and tissues. The area under the ROC curve of serum miR‐138‐5p in the diagnosis of NSCLC was 0.922. This finding indicates the high diagnostic efficiency for lung cancer. MiR‐138‐5p suppressed but its inhibitor promoted cell proliferation and migration compared with control treatment in vitro and in vivo. MiR‐138‐5p directly binds to the 3′‐untranslated region of SNIP1 and negatively regulated the expression of SNIP1, thereby inhibiting the expression of cyclin D1 and c‐Myc. Moreover, overexpression of SNIP1 rescues the miR‐138‐5p‐mediated inhibition in NSCLC cells. Conclusions The results suggested that miR‐138‐5p suppressed lung cancer cell proliferation and migration by targeting SNIP1. Serum miR‐138‐5p is a novel and valuable biomarker for NSCLC diagnosis.

Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at the Bact state, an active spliceosome but not catalytically primed, which depends on Smad Nuclear Interacting Protein 1 (SNIP1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing, and that its misregulation contributes to neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) play crucial roles in the development of various cancers. Here, we aimed to evaluate the roles of miR‐138‐5p in lung cancer progression and the value of miR‐138‐5p in lung cancer diagnosis. Methods: Quantitative real‐time PCR was performed to examine the expressions of miR‐138‐5p and smad nuclear interacting protein 1 (SNIP1) mRNA. The diagnostic value of miR‐138‐5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. We explored the effect of miR‐138‐5p on cell proliferation and metastasis by CCK‐8, colony formation, wound healing and transwell assays. Western blot was employed to detect the protein expression of SNIP1 and related genes. Lung cancer cell growth was evaluated in vivo using xenograft tumor assay. Results: MiR‐138‐5p was decreased in the serum of patients with non‐small cell lung cancer (NSCLC) and in NSCLC cells and tissues. The area under the ROC curve of serum miR‐138‐5p in the diagnosis of NSCLC was 0.922. This finding indicates the high diagnostic efficiency for lung cancer. MiR‐138‐5p suppressed but its inhibitor promoted cell proliferation and migration compared with control treatment in vitro and in vivo. MiR‐138‐5p directly binds to the 3′‐untranslated region of SNIP1 and negatively regulated the expression of SNIP1, thereby inhibiting the expression of cyclin D1 and c‐Myc. Moreover, overexpression of SNIP1 rescues the miR‐138‐5p‐mediated inhibition in NSCLC cells. Conclusions: The results suggested that miR‐138‐5p suppressed lung cancer cell proliferation and migration by targeting SNIP1. Serum miR‐138‐5p is a novel and valuable biomarker for NSCLC diagnosis. [ABSTRACT FROM AUTHOR]

The TET2 DNA dioxygenase regulates gene expression by catalyzing demethylation of 5-methylcytosine, thus epigenetically modulating the genome. TET2 does not contain a sequence-specific DNA-binding domain, and how it is recruited to specific genomic sites is not fully understood. Here we carried out a mammalian two-hybrid screen and identified multiple transcriptional regulators potentially interacting with TET2. The SMAD nuclear interacting protein 1 (SNIP1) physically interacts with TET2 and bridges TET2 to bind several transcription factors, including c-MYC. SNIP1 recruits TET2 to the promoters of c-MYC target genes, including those involved in DNA damage response and cell viability. TET2 protects cells from DNA damage-induced apoptosis dependending on SNIP1. Our observations uncover a mechanism for targeting TET2 to specific promoters through a ternary interaction with a co-activator and many sequence-specific DNA-binding factors. This study also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response, thereby connecting epigenetic control to maintenance of genome stability.

Inflammatory bowel disease (IBD) is a common inflammation-related intestinal disease. Studies have shown that excessive pyroptosis of intestinal cells is involved in the development of IBD. However, the regulatory mechanism of pyroptosis in IBD remains unclear. Here, our study purposed to clarify the underlying regulatory mechanism of miR-223 to promote pyroptosis in IBD. MiR-223 and Smad Nuclear Interacting Protein 1 (SNIP1) expression in colon tissues collected from IBD patients and healthy volunteers were evaluated using qRT-PCR. Cell viability and pyroptosis were evaluated by CCK8 and flow cytometry assay, respectively. Pyroptosis-related proteins and nuclear factor κB (NF-κB) signals were determined by WB. Dual-luciferase reporter gene assay was employed to investigate the binding relationship between miR-223 and SNIP1. MiR-223 was significantly upregulated in IBD colon tissues and cell models, while SNIP1 was significantly decreased. Silence of miR-223 markedly enhanced cell viability and inhibited pyroptosis in the IBD cell model. MiR-223 could bind to 3’-UTR of SNIP1 and SNIP1 could activate NF-κB signalling pathway. Further rescued experiment found that knockdown of SNIP1 dramatically abolished the bio-effects mediated by miR-223 silence on the cell viability and pyroptosis of the IBD cell model. Likewise, the inactivation of NF-κB signalling markedly weakened the regulatory roles of SNIP1 downregulation in the IBD cell model. Besides, inhibition of NF-κB signalling attenuated the pyroptosis-promoting effect of overexpressing miR-223. Our data suggested that miR-223 activated the NF-κB pathway via targeting SNIP1, thus promoting the process of cell pyroptosis, and ultimately participating in the pathogenesis of IBD.

As a common complication of Crohn's disease (CD), the mechanism underlying CD intestinal fibrosis remains unclear. Studies have shown that epithelial-mesenchymal transition (EMT) is a key step in the development of intestinal fibrosis in CD. It is currently known that the long non-coding RNA (lncRNA) MSC-AS1 plays an important role in regulating the secretion of inflammatory mediators and EMT; however, its role in intestinal fibrosis remains unclear. MSC-AS1 was significantly upregulated in the CD intestinal tissue and intestinal tissue of mice treated with 2,4,6-trinitrobenzenesulfonic acid. Downregulation of its expression can inhibit EMT and alleviates intestinal fibrosis by regulating SNIP1. In addition, MSC-AS1 directly interacted with SENP1, blocking the deSUMOylation of SNIP1 and inhibiting its activity. Furthermore, we found that SENP1 enhanced the expression of SNIP1 and reduced intestinal fibrosis. In summary, MSC-AS1 regulates EMT through the SENP1/SNIP1 axis to promote fibrosis, and may be considered a potential molecular target for the treatment of CD and intestinal fibrosis. [ABSTRACT FROM AUTHOR]

Smad nuclear interacting protein 1 (SNIP1) is a nuclear protein and involved in essential biological processes. MicroRNAs are effective regulators of tumorigenesis and cancer progression via targeting multiple genes. In present study, we aimed to investigate the function of SNIP1 and identify novel miRNA-SNIP1 axis in the development of cervical cancer. The results showed for the first time that silencing of the SNIP1 gene inhibited the migration and proliferation in HeLa cells significantly. Bioinformatics analysis and dual luciferase reporter assay demonstrated that miR-29a-3p could target 3′ UTR of SNIP1 directly. The mRNA and protein expression levels of SNIP1 were negative regulated by miR-29a-3p according to the RT-qPCR and Western blot analysis, respectively. Furthermore, functional studies showed that over-expression of miR-29a-3p restrained HeLa cells migration and proliferation, and the mRNA expression of SNIP1 downstream genes (HSP27, c-Myc, and cyclin D1) were down-regulated by miR-29a-3p. Together, we concluded that miR-29a-3p suppressed the migration and proliferation in HeLa cells by directly targeting SNIP1. The newly identified miR-29a-3p/SNIP1 axis could provide new insight into the development of cervical cancer.

Acute pancreatitis (AP) is the inflammatory response of the exocrine pancreas to various causes. Modafinil has significant anti-inflammation and anti-oxidation effects. No experiment has assessed the effects of modafinil on AP. Thus, the study aims to study the effects of modafinil on AP and its potential mechanism in vivo and vitro. 5% sodium taurocholate was retrograde injected into pancreatic duct to establish AP rat model. The severity of AP was detected by H&E staining, serum amylase and lipase levels. The inflammation, oxidative stress and apoptosis were detected separately by ELISA, MDA and SOD kits, tunnel staining and Western blotting in rats. Besides, SNIP1 expression was analyzed by qPCR and Western blotting. In vivo, AR42J cells were stimulated by cerulein and lipopolysaccharide to establish AP cell model. Flow cytometry examined cell apoptosis. After the plasmids silencing SNIP1 were transfected into AP cells, the inhibitory effects of modafinil on inflammation, oxidative stress and apoptosis were significantly reversed. The results indicated that modafinil showed significant curative and therapeutic effects by regulating SNIP1 levels. [ABSTRACT FROM AUTHOR]

Smad intranuclear binding protein 1 (SNIP1), a highly conserved nuclear protein, functions as a transcriptional regulator and exerts a significant influence on disease progression. In addition, the N-terminal domain of SNIP1 facilitates its interaction with Smad4, a signaling protein associated with the TGF-β family, and RelA/p65, a transcription factor connected to NF-κB. This interaction further enhances the transcriptional activation of c-Myc-dependent genes. Presently, the primary emphasis in research is directed towards targeting the catalytic domain of SNIP1, as it holds promise as a potential therapeutic target for various diseases. While the significance of SNIP1 in pathological mechanisms remains uncertain, this review aims to comprehensively examine the existing literature on the association between SNIP1 and proteins implicated in the regulation of diverse clinical conditions, including cancer, inflammation, and related diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Some rare earth elements are occupational and environmental toxicants and can cause organ and systemic damage; therefore, they have attracted global attention. Neodymium oxide (Nd2O3) is a rare earth element that is refined and significantly utilized in China. The long noncoding RNA (lncRNA) H19 is encoded by the H19/IGF2 imprinted gene cluster located on human chromosome 11p15.5. H19 has become a research focus due to its ectopic expression leading to the promotion of fibrosis. However, the mechanisms by which it causes pulmonary fibrosis are elusive. This investigation indicates that biologically active Nd2O3 increases H19, SNIP1, and c-myc, decreases miR-29a-3p, accelerates macrophage M2 polarization, and causes pulmonary fibrosis in mice lung tissues. In macrophage-differentiated THP-1 cells, Nd2O3 (25 μg/ml) enhanced H19, SNIP1, and c-myc, reduced miR-29a-3p, accelerated macrophages M2 polarization, and stimulated fibrogenic cytokine (TGF-β1) secretion. Furthermore, the coculturing of Nd2O3-treated macrophage-differentiated THP-1 cells. And human embryonic lung fibroblast cells activated lung fibroblast, which increases the levels of collagen I, α-SMA, p-Smad2/3, and Smad4, whereas H19 knockdown or miR-29a-3p upregulation in macrophages had opposite effects. Moreover, it was revealed that H19/miR-29a-3p/SNIP1/c-myc regulatory axis is involved in pulmonary fibrosis induced by Nd2O3. Therefore, this study provides new molecular insights into the mechanism of pulmonary fibrosis by Nd2O3., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Osteoarthritis (OA), the most common joint disease, is characterized by inflammation and cartilage degradation. Previous studies illustrated that Smad nuclear-interacting protein 1 (SNIP1) is an inhibitor of the TGF-β signal transduction pathway and SNIP1 has been reported as an anti-inflammatory factor. This study aimed to explore the role of SNIP1 in OA progression. In this study, the SNIP1 expression was evaluated in OA human and OA mice tissue and interleukin-1 beta (IL-1β)-induced chondrocytes. The Safranin-O (SO) staining and osteoarthritis research society international (OARSI) scoring system was used to evaluate cartilage injury. The gain- and loss-of-function studies for SNIP1 were performed in chondrocytes. The SNIP1 overexpression adenovirus was injected into mice by intra-articular injection. The SNIP1 expression was decreased in OA patients, OA mice, and IL-1β-stimulated chondrocytes. The cartilage injury of medial meniscus-induced OA (DMM-OA) mice at 8 weeks showed more severe than that at 4 weeks. The expression of SNIP1 was lower at 8 weeks than that at 4 weeks. In IL-1β-stimulated chondrocytes, SNIP1 overexpression reduced the expression of TNF-α and IL-6, alleviated ECM degradation, reduced the phosphorylation levels of p65 and IκBα, and decreased the p65 level in nuclear. Moreover, overexpression of SNIP1 alleviated cartilage injury in DMM-OA mice. In brief, our study suggested that SNIP1 alleviated OA and repressed inflammation by inhibiting the activation of NF-κB. This study might provide a new insight into OA treatment. [Display omitted] • SNIP1 expression was downregulated in OA tissues. • High expression of SNIP1 inhibited inflammation in chondrocytes. • SNIP1 inhibited the NF-κB pathway to reduced inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Interstitial microdeletions of chromosome 1p34.3p34.2 are rare, but are continuing to be identified by the use of chromosome microarray. There have been fewer than 10 individuals identified who have deletions of the 1p34.3p34.2 region; all of these previously described individuals have deletions of the AGO1, AGO3, GRIK3, SLC2A1, or RIMS3 genes. Haploinsufficiency of these genes has been associated with neurodevelopmental delays. Methods: Chromosome microarray, quantitative PCR, and fluorescence in situ hybridization were performed with DNA extracted from peripheral blood. Results: Chromosome microarray identified a 2.3 Mb 1p34.3p34.2 one copy deletion in our patient with global developmental delay, mild intellectual disability, delayed bone age, bilateral vesicoureteral reflux, vocal cord paralysis, right aberrant subclavian artery, kyphoscoliosis, bilateral metatarsus adductus, and valgus knee deformity. This deletion was confirmed by quantitative PCR and does not include the AGO1, AGO3, GRIK3, SLC2A1, or RIMS3 genes. Subsequent FISH testing of the parents was negative. Conclusion: Haploinsufficiency of the 1p34.3p34.2 region, including the SNIP1 gene and excluding the five genes listed above, is responsible for the neurocognitive delays and other symptoms as identified in our patient. [ABSTRACT FROM AUTHOR]

[Display omitted] The therapeutic activity of paclitaxel against ovarian carcinoma is relatively low due to the frequent occurrence of chemoresistance and disease recurrence. We found earlier that a combination of curcumin and paclitaxel reduces cell viability and promotes apoptosis in paclitaxel-resistant (i.e., taxol-resistant, Txr) ovarian cancer cells. In the present study, we first used RNA sequencing (RNAseq) analysis to identify genes that are upregulated in Txr cell lines but downregulated by curcumin in ovarian cancer cells. The nuclear factor kappa B (NFκB) signaling pathway was shown to be upregulated in Txr cells. Furthermore, based on the protein interaction database BioGRID, we found that Smad nuclear interacting protein 1 (SNIP1) may be involved in regulating the activity of NFκB in Txr cells. Accordingly, curcumin upregulated SNIP1 expression, which in turn downregulated the pro-survival genes Bcl-2 and Mcl-1. Using shRNA-guided gene silencing, we found that SNIP1 depletion reversed the inhibitory effect of curcumin on NFκB activity. Moreover, we identified that SNIP1 enhanced NFκB protein degradation, thereby suppressing NFκB/p65 acetylation, which is involved in the inhibitory effect of curcumin on NFκB signaling. The transcription factor early growth response protein 1 (EGR1) was shown to represent an upstream transactivator of SNIP1. Consequently, we show that curcumin inhibits NFκB activity by modulating the EGR1/SNIP1 axis to attenuate p65 acetylation and protein stability in Txr cells. These findings provide a new mechanism to account for the effects of curcumin in inducing apoptosis and reducing paclitaxel resistance in ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) can have a critical function in the multi-processes of osteosarcoma (OS). Nevertheless, whether circUSP48 is involved in OS progression remains unclear., Methods: In the current work, the expression of circUSP48, miR-335 and SNIP1 in OS cell lines and tissues were evaluated using qRT-PCR. Then, Sanger sequencing, RNase R treatment and FISH assay were performed for circUSP48 validation. Furthermore, the function and potential mechanisms of circUSP48 in OS were investigated by performing loss-of-function experiments., Results: Silencing circUSP48 could suppress proliferation, invasion as well as migration of OS cells in vitro, also inhibiting the growth of tumor in vivo. Importantly, circUSP48 promoted OS malignancy by sponging miR-335 to upregulate SNIP1., Conclusion: Overall, these findings suggested that circUSP48 acted as an oncogene in OS, which might become a new target for OS therapy., (© 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Abstract: The Rb tumor suppressor gene performs a critical role in controlling cell proliferation and tumorigenesis; it recruits HDAC1 protein into the E2F complexes to repress transcription. In this study, we demonstrate that SNIP1, RB and HDAC1 were significantly expressed in same lung cancer tissues in a tissue microarray (TMA) containing 300 non-small cell lung cancers (NSCLC). High expression level of SNIP1 in tumor patients was significantly correlated with poor prognosis in NSCLC (log-rank P for OS=0.01, log-rank P for DFS=0.001). Functionally, SNIP1 competes with HDAC1 for binding to RB and reduces HDAC activity in vitro. Knockdown of SNIP1 reduced colony formation ability of lung cancer cells. These findings may indicate the involvement of SNIP1 in progression of lung cancer by regulating the RB/HDAC1 interaction. [Copyright &y& Elsevier]

Smad nuclear interacting protein 1 (SNIP1) gene encodes a protein that contains a conservative C-terminal forkhead-associated domain and functions as a transcriptional coactivator to regulate cell proliferation and cancer progression. This study aimed to investigate the clinical and biological significance of SNIP1 expression in pituitary adenoma. We analyzed SNIP1 expressions in mouse fibroblast L929 cells and mouse pituitary adenoma AtT-20 cells by Western blotting. SNIP1 gene knockdown by small interfering RNA (siRNA) transfection was performed to evaluate SNIP1 function in pituitary adenoma cell lines. As expected, SNIP1 was found to be upregulated in pituitary adenoma cells. The mRNA and protein levels of SNIP1 were inhibited in AtT-20 cells transfected with siRNAs, which led to decreased proliferation, increased apoptosis, and cycle arrest of pituitary adenoma cells. Concomitantly, c-Myc and cyclin D1 protein levels were reduced. These findings may provide novel targets for the treatment of pituitary adenoma. [ABSTRACT FROM AUTHOR]

Abstract: A Smad nuclear interacting protein 1 (SNIP1) homologous gene was identified in amphioxus. Phylogenic analysis showed that SNIP1 proteins from different species share a highly conserved FHA domain at the C-terminus, but their N-terminus varies remarkably. The genomic structure of SNIP1 varies in different species, especially at the 5′ end. Through in situ hybridization, we studied SNIP1 expression patterns in amphioxus and zebrafish embryos. Amphioxus SNIP1 transcripts were specifically located in the notochord in larval and adult stages. In zebrafish, however, snip1 transcripts were specifically located not only in the notochord, but also in the rhombencephalic ventricle, otic vesicles and pectoral fin buds. This is the first report of SNIP1 expression pattern in early development, which clearly shows different expression patterns between invertebrates and vertebrates. Previous studies reported that it is the N-terminal domain of human and mouse SNIP1 that functions to inhibit both TGF-ß and the NF-κB pathways. Therefore, it is most likely that the modification of SNIP1 expression pattern is related to the remarkable evolution in the N-terminal sequence. In addition, the difference in SNIP1 expression pattern between amphioxus and zebrafish implies the role of SNIP1 in the vertebrate body structural innovation of brain, otic vesicles and pectoral fins. [Copyright &y& Elsevier]

In the last 10 years, more and more attention has been focused on SNIP1 (Smad nuclear interacting protein 1), which functions as a transcriptional coactivator. We report here that through quantitative real-time PCR analysis in 18 different human tissues, SNIP1 was found to be expressed ubiquitously. When overexpressed in HeLa cells, SNIP1-EGFP fused protein exhibited a nuclear localization with a characteristic subnuclear distribution in speckles or formed larger discrete nuclear bodies in some cells. Reporter gene assay showed that overexpression of SNIP1 in HEK 293 cells or H1299 cells strongly activated the HSE signaling pathway. Moreover, SNIP1 could selectively regulate the transcription of HSP70A1A and HSP27. Taken together, our findings suggest that SNIP1 might also be a positive regulator of HSE signaling pathway. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a common inflammation-related intestinal disease. Studies have shown that excessive pyroptosis of intestinal cells is involved in the development of IBD. However, the regulatory mechanism of pyroptosis in IBD remains unclear. Here, our study purposed to clarify the underlying regulatory mechanism of miR-223 to promote pyroptosis in IBD.MiR-223 and Smad Nuclear Interacting Protein 1 (SNIP1) expression in colon tissues collected from IBD patients and healthy volunteers were evaluated using qRT-PCR. Cell viability and pyroptosis were evaluated by CCK8 and flow cytometry assay, respectively. Pyroptosis-related proteins and nuclear factor κB (NF-κB) signals were determined by WB. Dual-luciferase reporter gene assay was employed to investigate the binding relationship between miR-223 and SNIP1.MiR-223 was significantly upregulated in IBD colon tissues and cell models, while SNIP1 was significantly decreased. Silence of miR-223 markedly enhanced cell viability and inhibited pyroptosis in the IBD cell model. MiR-223 could bind to 3'-UTR of SNIP1 and SNIP1 could activate NF-κB signalling pathway. Further rescued experiment found that knockdown of SNIP1 dramatically abolished the bio-effects mediated by miR-223 silence on the cell viability and pyroptosis of the IBD cell model. Likewise, the inactivation of NF-κB signalling markedly weakened the regulatory roles of SNIP1 downregulation in the IBD cell model. Besides, inhibition of NF-κB signalling attenuated the pyroptosis-promoting effect of overexpressing miR-223.Our data suggested that miR-223 activated the NF-κB pathway via targeting SNIP1, thus promoting the process of cell pyroptosis, and ultimately participating in the pathogenesis of IBD.

Smad nuclear interacting protein 1 (SNIP1) is a nuclear protein and involved in essential biological processes. MicroRNAs are effective regulators of tumorigenesis and cancer progression via targeting multiple genes. In present study, we aimed to investigate the function of SNIP1 and identify novel miRNA-SNIP1 axis in the development of cervical cancer. The results showed for the first time that silencing of the SNIP1 gene inhibited the migration and proliferation in HeLa cells significantly. Bioinformatics analysis and dual luciferase reporter assay demonstrated that miR-29a-3p could target 3' UTR of SNIP1 directly. The mRNA and protein expression levels of SNIP1 were negative regulated by miR-29a-3p according to the RT-qPCR and Western blot analysis, respectively. Furthermore, functional studies showed that over-expression of miR-29a-3p restrained HeLa cells migration and proliferation, and the mRNA expression of SNIP1 downstream genes ( HSP27 , c-Myc , and cyclin D1 ) were down-regulated by miR-29a-3p. Together, we concluded that miR-29a-3p suppressed the migration and proliferation in HeLa cells by directly targeting SNIP1. The newly identified miR-29a-3p/SNIP1 axis could provide new insight into the development of cervical cancer., Competing Interests: The authors declare there are no competing interests., (©2020 Chen et al.)

SNIP1 (Smad nuclear interacting protein 1) is a transcription repressor for the TGF-β and NF-κB signaling pathways through disrupting the recruitment of co-activator p300. However, it is unclear how the functions of SNIP1 in the TGF-β signaling pathway are controlled. Our present studies show that SNIP1 is covalently modified by small ubiquitin-like modifier (SUMO) in vitro and in vivo at three lysine sites: Lys 5 , Lys 30 , and Lys 108 , with Lys 30 being the major SUMO modification site. SUMOylation of SNIP1 is enhanced by SUMO E3 ligase PIAS proteins and inhibited by SUMO proteases SENP1/2. Furthermore, we find that SUMOylation of SNIP1 attenuates its inhibitory effect in TGF-β signaling because the SUMO-conjugated form of SNIP1 exhibits impaired ability to disrupt the formation of Smad complex and the interaction between p300 and Smads. Subsequently, SUMOylation of SNIP1 leads to the loss of SNIP1-mediated inhibition on expression of the TGF-β target genes PAI-1 and MMP2 and eventually enhances TGF-β-regulated cell migration and invasion., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)