Small Nucleolar RNA Host Gene Research Articles

LncRNA SNHG11 accelerates the progression of lung adenocarcinoma via activating Notch pathways

BackgroundNumerous researches have emphasized that long non-coding RNAs (lncRNAs) have a close association with the biological process in multiple cancers including lung adenocarcinoma (LUAD). Nevertheless, the detailed function and potential mechanism of Small nucleolar RNA Host Gene 11 (SNHG11) in LUAD keep unknown. MethodsQuantitative reverse transcription polymerase chain reaction (RT-qPCR) tested SNHG11, miR-193a-5p and notch receptor 3 (Notch3) expression. Functional assays tested the function of SNHG11 in LUAD cells. The relationship among SNHG11, miR-193a-5p and Notch3 was verified by mechanism assays. In vivo assays were implemented to reveal the role of SNHG11 in LUAD tumor growth. ResultsSNHG11 was evidently high expressed in LUAD cells in comparison to normal lung epithelial cells. Moreover, down-regulation of SNHG11 hindered viability, proliferation and migration of LUAD cells as well as tumor growth. As for the mechanisms, SNHG11 activated Notch pathway via regulating Notch3. In addition, SNHG11 competitively bound with miR-193a-5p to up-regulate Notch3. The last rescue assays displayed that SNHG11 affecting LUAD cell malignant behaviors via regulating miR-193a-5p/SNHG11. ConclusionSNHG11 regulated miR-193a-5p/Notch3 axis to activate Notch pathway, consequently facilitating the proliferation and migration in LUAD.

Role and mechanism of the lncRNA SNHG1/miR‑450b‑5p/IGF1 axis in the regulation of myocardial ischemia reperfusion injury.

The increasing rates of morbidity and mortality caused by ischemic heart disease pose a serious threat to human health. Long non-coding (lnc)RNA small nucleolar RNA host gene 1 (SNHG1) has a protective effect on the myocardium. In the present study, the role of lncRNA SNHG1 in myocardial ischemia reperfusion injury (MIRI) and the underlying mechanisms were investigated. After hypoxia/reoxygenation (H/R) induction, the expression levels of lncRNA SNHG1 were detected using reverse transcription-quantitative PCR. After lncRNA SNHG1 overexpression via cell transfection, cell viability was detected using an MTT assay, apoptotic rates were detected using TUNEL staining, apoptosis-related protein expression levels were detected using western blotting and respective kits were used to measure the oxidative stress levels. The Encyclopedia of RNA Interactomes database predicted the presence of binding sites between lncRNA SNHG1 and microRNA (miR)-450b-5p, and between miR-450b-5p and insulin-like growth factor 1 (IGF1). These interactions were then verified using luciferase reporter assays. Subsequently, the regulatory mechanism underlying the lncRNA SNHG1/miR-450b-5p/IGF1 axis in MIRI was investigated by overexpressing miR-450b-5p and knocking down IGF1 expression in H/R-induced cells. Finally, the expression of PI3K/Akt signaling pathway-related proteins was detected using western blotting. lncRNA SNHG1 expression was significantly downregulated in H/R-induced AC16 cells. lncRNA SNHG1 overexpression significantly inhibited apoptosis and decreased oxidative stress levels in H/R-induced AC16 cells, which was mediated via regulation of the miR-450b-5p/IGF1 axis and activation of the PI3K/Akt signaling pathway. Therefore, the present study suggested that activation of the PI3K/Akt signaling pathway via the lncRNA SNHG1/miR-450b-5p/IGF1 axis inhibited the apoptosis and oxidative stress levels of H/R-induced AC16 cells.

Vitamin D May Protect against Breast Cancer through the Regulation of Long Noncoding RNAs by VDR Signaling.

Dietary vitamin D3 has attracted wide interest as a natural compound for breast cancer prevention and therapy, supported by in vitro and animal studies. The exact mechanism of such action of vitamin D3 is unknown and may include several independent or partly dependent pathways. The active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D, calcitriol), binds to the vitamin D receptor (VDR) and induces its translocation to the nucleus, where it transactivates a myriad of genes. Vitamin D3 is involved in the maintenance of a normal epigenetic profile whose disturbance may contribute to breast cancer. In general, the protective effect of vitamin D3 against breast cancer is underlined by inhibition of proliferation and migration, stimulation of differentiation and apoptosis, and inhibition of epithelial/mesenchymal transition in breast cells. Vitamin D3 may also inhibit the transformation of normal mammary progenitors into breast cancer stem cells that initiate and sustain the growth of breast tumors. As long noncoding RNAs (lncRNAs) play an important role in breast cancer pathogenesis, and the specific mechanisms underlying this role are poorly understood, we provided several arguments that vitamin D3/VDR may induce protective effects in breast cancer through modulation of lncRNAs that are important for breast cancer pathogenesis. The main lncRNAs candidates to mediate the protective effect of vitamin D3 in breast cancer are lncBCAS1-4_1, AFAP1 antisense RNA 1 (AFAP1-AS1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), long intergenic non-protein-coding RNA 511 (LINC00511), LINC00346, small nucleolar RNA host gene 6 (SNHG6), and SNHG16, but there is a rationale to explore several other lncRNAs.

SNHG1-miR-186-5p-YY1 feedback loop alleviates hepatic ischemia/reperfusion injury

ABSTRACT As a common cause of liver injury, hepatic ischemia/reperfusion injury (HIRI) happens in various clinical conditions including trauma, hepatectomy and liver transplantation. Since transcription factor Yin Yang 1 (YY1) was reported to be downregulated after ischemia/reperfusion (I/R) injury, we focused on YY1 to explore its function in HIRI by functional assays like Cell Counting Kit-8 (CCK-8) assays and flow cytometry assays. The RT-qPCR assay revealed that YY1 was downregulated in hepatocytes after I/R injury. The function assays disclosed that YY1 facilitated cell viability and proliferation, but hindered cell apoptosis in hepatocytes after I/R injury. Through mechanism assays including luciferase reporter assay, RIP and RNA pulldown assay, miR-186-5p was found to bind with YY1 and promote hepatocyte apoptosis by targeting YY1. Subsequently, we verified that small nucleolar RNA host gene 1 (SNHG1) could sponge miR-186-5p to upregulate YY1. Importantly, we figured out that YY1 had a positive regulation on SNHG1. Along the way, YY1 was identified as the upstream transcription factor for SNHG1. In conclusion, our study unveiled a novel competing endogenous RNA (ceRNA) pattern of SNHG1/miR-186-5p/YY1 positive feedback loop in hepatic I/R injury, which might provide new insight into prevention of HIRI during liver transplantation or hepatic surgery.

LncRNA SNHG1 Delayed Fracture Healing via Modulating miR-181a-5p/PTEN Axis

Background:The purpose of this study was to investigate the role of Long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in delayed healing of tibial fractures and its potential regulatory mechanisms. Methods: 51 patients with normal healing of tibial fractures and 46 patients with delayed healing of tibial fractures were enrolled. RT-qPCR was performed to analyze SNHG1, microRNA (miRNA)-181a-5p, and PTEN levels. ROC curves were used to detect the predictive value of SNHG1 for delayed healing in fracture patients. Subsequently, the regulation of osteogenic markers by SNHG1 and miR-181a-5p was analyzed in MC3T3-E1. Cell proliferation and apoptosis were quantified by CCK-8 and flow cytometry. The binding between SNHG1/miR-181a-5p/PTEN was detected by dual-luciferase reporter gene assay. Results: Serum SNHG1 and PTEN expression were upregulated and miR-181a-5p expression was downregulated in patients with delayed fracture healing. SNHG1 decreased the level of osteogenic markers in MC3T3-E1, inhibited the proliferation, and stimulated apoptosis of MC3T3-E1 (P < 0.05). SNHG1 acted as a sponge for miR-181a-5p, and elevation of miR-181a-5p abolished the inhibition of osteogenic differentiation and promotion of apoptosis by SNHG1 (P < 0.05). PTEN was identified as a target of miR-181a-5p and involved in this regulatory process. Finally, elevated SNHG1 was a feasible predictive biomarker in patients with delayed fracture healing. Conclusion: The current study revealed that SNHG1/miR-181a-5p/PTEN axis inhibited osteoblast differentiation and proliferation and promoted apoptosis, thus leading to the inhibition of tibial fracture healing. Our findings contribute to the understanding of the mechanisms underlying delayed tibial fracture healing.

LncRNA small nucleolar RNA host gene 5 inhibits trophoblast autophagy in preeclampsia by targeting microRNA-31-5p and promoting the transcription of secreted protein acidic and rich in cysteine

ABSTRACT Preeclampsia (PE) is a pregnancy-related complication. Dysregulation of long non-coding RNAs (lncRNAs) contributes to the pathogenesis of PE. The current study sought to investigate the effect of lncRNA small nucleolar RNA host gene 5 (SNHG5) on trophoblast autophagy in PE. A PE mouse model was established, followed by detection of parameters such as blood pressure, proteinuria, triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein, observation of alterations of mouse placenta and kidney, and detection of B-cell chronic lymphocytic leukemia/lymphoma-2, Bcl-2-associated X protein, and SNHG5 expression patterns. The expressions of LC3, Beclin-1, and p62 in the placenta of PE mice were detected. Moreover, the SNHG5 expression was downregulated in the established HTR-8/SVneo trophoblast model, followed by evaluation of cell proliferation, apoptosis, and autophagy. After combination treatment with 3-MA (an autophagy inhibitor) and si-SNHG5, the behaviors of HTR-8/SVneo cells were observed. The binding relations between SNHG5 and miR-31-5p, and miR-31-5p and SPARC were verified. The expressions of miR-31-5p and SPARC in the placenta of mice and trophoblasts were determined. Our results demonstrated a poor expression of lncRNA SNHG5 in PE mice. SNHG5 overexpression reduced the PE phenotype and tissue damage in mice. SNHG5 silencing reduced the proliferation, migration, and invasion of trophoblasts, but elevated apoptosis and autophagy. SNHG5 sponged miR-31-5p to promote SPARC transcription. Additionally, miR-31-5p knockdown or 3-MA treatment reverted the stimulative effect of SNHG5 silencing on trophoblast autophagy. Collectively, our study demonstrated that lncRNA SNHG5 alleviated the PE phenotype and inhibited trophoblast autophagy by sponging miR-31-5p and promoting SPARC transcription.

RBM47/SNHG5/FOXO3 axis activates autophagy and inhibits cell proliferation in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the main type of thyroid carcinoma. Despite the good prognosis, some PTC patients may deteriorate into more aggressive diseases, leading to poor survival. Molecular technology has been increasingly used in the diagnosis and treatment of thyroid carcinoma. In this study, we identified that RNA Binding Motif Protein 47 (RBM47) was downregulated in PTC tissues and cells, and overexpression of RBM47 could activate autophagy and inhibit proliferation in PTC cells. RBM47 promotes but can not bind directly to Forkhead Box O3 (FOXO3). FOXO3 activates Autophagy Related Gene 3 (ATG3), ATG5, and RBM47 to form a loop and promote autophagy. RBM47 can bind directly to and stabilized lncRNA Small Nucleolar RNA Host Gene 5 (SNHG5) to inhibit PTC cells proliferation and activate autophagy in vitro and in vivo. SNHG5 inhibits ubiquitination and degradation of FOXO3 by recruiting Ubiquitin Specific Peptidase 21 (USP21), then promotes the translocation of FOXO3 from cytoplasm to nucleus. Our study revealed the regulatory mechanism of RBM47/SNHG5/FOXO3 axis on cell proliferation and autophagy in PTC, which may provide valuable insight for the treatment of PTC.

PMN Apoptosis Induced by SNHG11 through the Inhibition of Endotoxin-induced Acute Lung Injury NF-κB Pathway.

To investigate the impacts of small nucleolar RNA host gene 11 (SNHG11) on nuclear factor kappa-B (NF-κB) pathway and polymorphonuclear granulocyte (PMN) apoptosis in rats with endotoxin-induced acute lung injury (ALI). Forty rats were the experimental subjects. They were randomly grouped as a control group (Group C), an endotoxin group (Group E), an inhibitor group (Group I), and an activator group (Group A), with 10 rats in each group. The endotoxin-educed ALI rat model was built. Arterial Blood Gas Test (ABGT) was performed, and the Wet/Dry (W/D) ratio of lung weight was determined. The pathological variations in rat pulmonary tissues were scrutinized and scored. PMN in peripheral blood was isolated; its apoptosis was assessed, and its total NF-κB p65 and p-NF-κB p65 expressions were assessed. The expression of SNHG11 mRNA in pulmonary tissues was assessed. Results: Compared to Group C, the W/D ratios and pathological scores of Group E, Group I, and Group A boosted notably (P <0.05), while their ABGT indicators and PMN apoptosis rates dropped (P <0.05). Compared to Group E and Group I, the W/D ratio and pathological score of Group A dropped notably (P <0.05), while its ABGT indicators and PMN apoptosis rate boosted (P <0.05). Compared to Group C, the p-NF-κB p65 and SNHG11 expressions were boosted in Group E, Group I, and Group A (P <0.05); compared to Group E and Group I, the p-NF-κB p65 and SNHG11 expressions in Group A dropped (P <0.05). SNHG11 could relieve endotoxin-induced ALI, which might be associated with the acceleration of PMN apoptosis and the inhibition of the NF-κB pathway.

LncRNA SNHG15: A potential therapeutic target in the treatment of colorectal cancer.

The global burden of colorectal cancer (CRC) is increasing annually. CRC could develop from genetic and phenotypic factors involving changes in gene expression. Incredibly, the human genome transcribes into non-coding RNAs, among which long non-coding RNAs (lncRNAs) signify the most crucial part of the transcriptome in multicellular organisms. lncRNAs affect gene expression at multiple levels, from transcription to protein localization and stability. Recent studies have implicated lncRNA small nucleolar RNA host gene 15 (SNHG15) in cancers occurrence and progression. Previously, an indication suggests SNHG15 overexpression triggers proliferation, metastasis, and impedes apoptosis in CRC. Further, through its activity of binding micro-RNAs, lncRNA SNHG15modulates genes associated with CRC progression and promotes CRC resistance to chemotherapeutic drugs. Here, we reviewed recent findings on the various mechanisms and roles of lncRNA SNHG15 implicated in CRC tumorigenesis. We further highlight how SNHG15 plays a vital role in regulating critical pathways linked to the development and progression of CRC. Finally, we highlight how SNHG15 can be modulated for CRC treatments and the various therapeutic strategies to be implored when targeting SNHG15 in the context of CRC treatments. Findings from these studies present SNHG15 as a potential therapeutic target for preventing and treating CRC.

LncRNA small nucleolar RNA host gene 16 reduces sepsis-induced myocardial damage by regulating miR-421/suppressor of cytokine signaling 5 axis.

Currently, sepsis-induced cardiomyopathy (SIC) remains as one of the most critical clinical syndromes in terminally ill patients. Noncoding RNAs (including microRNAs and long noncoding RNAs) are implicated in both the onset and development of SIC. We herein investigated the functional role and molecular target of long noncoding RNA small nucleolar RNA host gene 16 (SNHG16) in an in vitro SIC model of H9c2 myocardial cells. We used lipopolysaccharide (LPS) as endotoxin to treat H9c2 cells to mimic SIC damages. Cell Counting Kit 8 and apoptosis assay were performed to assess cell proliferation and cell death. Quantitative real-time-PCR and Western blot were employed to examine gene expression level at mRNA and protein level. Dual luciferase assay is used to validate the functional interactions between SNHG16/mi-R421 and miR-421/suppressor of cytokine signaling 5 (SOCS5). Inflammatory cytokines were measured by ELISA. Superoxide dismutase and malondialdehyde measurement was performed to assess oxidative stress, which was further confirmed by 2',7'-dichlorofluorescin diacetate staining. Our data demonstrated that in the LPS-induced sepsis model of myocardial cells, SNHG16 overexpression downregulated the expression level of miR-421, which sustained the expression of SOCS5 to alleviate the adverse effects of LPS, such as apoptosis, pro-inflammatory cytokines, and oxidative stress. Our data suggest that SNHG16 functions as a ceRNA to maintain SOCS5 level by targeting miR-421, thereby attenuating LPS-induced myocardial cell damages. Targeting miR-421 or modulating lncRNA SNHG16 level may be leveraged as a beneficial strategy against sepsis-induced cellular damage in cardiomyocytes.

Mechanical force-sensitive lncRNA SNHG8 inhibits osteogenic differentiation by regulating EZH2 in hPDLSCs

Long non-coding RNAs (lncRNAs) play important roles in various physiological and pathophysiological processes. However, the effect of mechanical force on lncRNAs and their role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remains unclear. Here, we showed that the expression of lncRNA small nucleolar RNA host gene 8 (SNHG8) was steadily declined in PDLSCs under mechanical force. This reduced expression of SNHG8 promoted osteogenic differentiation of PDLSCs under mechanical force. After knockdown of SNHG8 by shRNA, the expression of osteogenic-related genes was increased in PDLSCs under mechanical force. Regarding the osteogenic regulatory ability of SNHG8, PDLSCs with lower level of expression of SNHG8 under osteogenic induction had a higher level of expression of osteogenic-related genes, higher level of alkaline phosphatase (ALP), and more mineralised nodules. In rats, the expression of the homolog, Smim4, was decreased during tooth movement. PDLSCs with lower expression of SNHG8 in nude mice also showed better bone formation ability during ectopic osteogenesis. Mechanistically, downregulation of SNHG8 led to lower expression of enhancer of zeste homolog 2 (EZH2), which negatively regulated the osteogenic differentiation of PDLSCs. Our study indicated that the mechanically sensitive lncRNA SNHG8 regulates the osteogenic differentiation of PDLSCs through epigenetic pathways. Our results provided solid evidence for the regulation of cell differentiation by non-coding genes, which might serve as potential therapeutic targets for bone reconstruction or periodontal tissue regeneration during orthodontics.

Mechanism of lncRNA SNHG16 in oxidative stress and inflammation in oxygen-glucose deprivation and reoxygenation-induced SK-N-SH cells

ABSTRACT Cerebral ischemia-reperfusion injury imposes a clinical challenge for physicians in the wake of ischemic stroke. Meanwhile, recent evidence has come to light eliciting the neuroprotective function of SNHG16 in cerebrovascular diseases. Accordingly, the current study sought to analyze the regulatory mechanism of long non-coding RNA small nucleolar RNA host gene16 (SNHG16) in oxidative stress (OS) injury and cell inflammation. Firstly, models of oxygen-glucose deprivation and reoxygenation (OGD/R) were established in SK-N-SH cells. Cell proliferation and apoptosis were appraised using cell counting kit-8 and flow cytometry. Additionally, SNHG16, X-linked inhibitor of apoptosis protein (XIAP), microRNA (miR-421), reactive oxygen species (ROS), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor -α, interleukin (IL)-1β, and IL-10 expression patterns were determined. In addition, we determined and validated the subcellular localization of SNHG16 and the binding relationships between SNHG16 and miR-421, and miR-421 and XIAP. It was found that SNHG16 was poorly-expressed in OGD/R-treated cells. On the other hand, SNHG16 over-expression enhanced cell proliferation, inhibited apoptosis, and alleviated OS and cell inflammation. Furthermore, SNHG16 bound to miR-421 to facilitate the expression of XIAP. Up-regulation of miR-421 or down-regulation of XIAP could reverse the suppressive effects of SNHG16 on OS and cell inflammation. Collectively, our findings indicated that SNHG16 bound to miR-421 to facilitate XIAP expression, thus alleviating OS injury and inflammation in OGD/R-induced SK-N-SH cells.

MicroRNA-363-3p, negatively regulated by long non-coding RNA small nucleolar RNA host gene 5, inhibits tumor progression by targeting Aurora kinase A in colorectal cancer

ABSTRACT MicroRNA-363-3p (miR-363-3p), reportedly, exhibits a tumor-suppressive role in human malignancies. Herein, our research was designed to further explain the functions and molecular mechanisms of miR-363-3p in the progression of colorectal cancer (CRC). With in vitro models, this study found that miR-363-3p was markedly under-expressed in CRC tissues and cells, and its overexpression suppressed the viability, migration, and invasion of CRC cells, and promoted cell apoptosis, whereas inhibiting miR-363-3p expression exhibited an opposite role. Additionally, aurora kinase A (AURKA), capable of counteracting the impacts of miR-363-3p on malignant biological behaviors of CRC cells, was identified as a direct target of miR-363-3p. Besides, miR-363-3p was sponged by long non-coding RNA small nucleolar RNA host gene 5 (SNHG5), which suppressed miR-363-3p expression. This research shows that SNHG5/miR-363-3p/AURKA axis partakes in CRC progression.

YY1-induced long non-coding RNA small nucleolar RNA host gene 8 promotes the tumorigenesis of melanoma via the microRNA-656-3p/SERPINE1 mRNA binding protein 1 axis

ABSTRACT Long non-coding (lnc) RNA serves a vital role in the cellular processes of carcinoma. This study aimed to explore the accurate mechanism underlying lncRNA small nucleolar RNA host gene 8 (SNHG8) in melanoma. In this study, lncRNA SNHG8 expression were upregulated in melanoma tissues and cells, and lncRNA SNHG8 knockdown reduced melanoma cell viability, migration and invasion. Moreover, lncRNA SNHG8 expression could be induced by transcription factor YY1. In addition, we found that miR-656 could directly bind to lncRNA SNHG8 and SERPINE1 mRNA binding protein 1 (SERBP1). Rescue assays indicated that miR-656 overexpression inhibited the aforementioned cellular activities in melanoma cells, which were reversed by SERBP1 overexpression. In conclusion, this work elucidated that YY1-induced upregulation of lncRNA SNHG8 boosted the development of melanoma via the miR-656-3p/SERBP1 axis, providing a novel therapeutic strategy for melanoma treatment.

Long non-coding RNA SNHG10 upregulates BIN1 to suppress the tumorigenesis and epithelial\u2013mesenchymal transition of epithelial ovarian cancer via sponging miR-200a-3p

Epithelial ovarian cancer (EOC) is one of the most frequent and fatal gynecologic malignant tumors resulting in an unsatisfying prognosis. Long non-coding RNAs (lncRNAs) play pivotal roles in the tumorigenesis and progression of EOC. However, the profile of lncRNAs involved in EOC remains to be expanded to further improve clinical treatment strategy. In present study, we identified a novel tumor-suppressive lncRNA small nucleolar RNA host gene 10 (SNHG10) in EOC. Kaplan–Meier analysis and COX proportional hazard progression model showed that low expression of SNHG10 was correlated with a poor prognosis of EOC patients. Overexpressing SNHG10 suppressed the proliferation, colony formation, migration, and invasion of EOC cells. Furthermore, SNHG10 was predicted to sponge miR-200a-3p in EOC cells according to the LncBase v.2 experimental module. Then, the binding of SNHG10 and miR-200a-3p was confirmed by performing quantitative real-time PCR (qRT-PCR) and luciferase reporter assays. RNA immunoprecipitation (RIP) showed that SNHG10 and miR-200a-3p occupied the same Ago2 protein to form an RNA-induced silencing complex (RISC). By overlapping the results from the bioinformatics algorithms, tumor-suppressor bridging integrator-1 (BIN1) was found to be a main downstream target of the SNHG10/miR-200a-3p axis. Low expression of BIN1 in EOC tissues was detected by using immunohistochemistry (IHC). Besides, BIN1 and SNHG10 expression was positively correlated in EOC tissues. By performing miRNA rescue experiments, a SNHG10/miR-200a-3p/BIN1 axis and its promoting effects on malignant behaviors and epithelial–mesenchymal transition (EMT) process were verified in EOC cells. Moreover, SNHG10 overexpression significantly suppressed the tumorigenesis and EMT of EOC cells in vivo. Altogether, SNHG10 sponges miR-200a-3p to upregulate BIN1 and thereby exerting its tumor-suppressive effects in EOC. Therefore, the SNHG10/miR-200a-3p/BIN1 axis may act as a potential predictive biomarker and therapeutic target for treating EOC.

Epithelial cells-enriched lncRNA SNHG8 regulates chromatin condensation by binding to Histone H1s.

Linker histone H1 proteins contain many variants in mammalian and can stabilize the condensed state of chromatin by binding to nucleosomes and promoting a more inaccessible structure of DNA. However, it is poorly understood how the binding of histone H1s to chromatin DNA is regulated. Screened as one of a collection of epithelial cells-enriched long non-coding RNAs (lncRNAs), here we found that small nucleolar RNA host gene 8 (SNHG8) is a chromatin-localized lncRNA and presents strong interaction and phase separation with histone H1 variants. Moreover, SNHG8 presents stronger ability to bind H1s than linker DNA, and outcompetes linker DNA for H1 binding. Consequently, loss of SNHG8 increases the amount of H1s that bind to chromatin, promotes chromatin condensation, and induces an epithelial differentiation-associated gene expression pattern. Collectively, our results propose that the highly abundant SNHG8 in epithelial cells keeps histone H1 variants out of nucleosome and its loss contributes to epithelial cell differentiation.

Potential diagnostic and prognostic value of the long non-coding RNA SNHG3 in human cancers: A systematic review and meta-analysis.

Small nucleolar RNA host gene 3 (SNHG3), as a novel long non-coding RNA (lncRNA) participates in the oncogenic processes of various cancers. We combined a systematic review and a meta-analysis to assess the potential role of SNHG3 as a pan-cancer marker for cancer diagnosis and prognosis. Our study comprehensively searched for SNHG3 expression profiling studies from PubMed, Web of Science, Excerpta Medica Database (EMBASE), Cochrane Library, Google Scholar, and The Cancer Genome Atlas (TCGA). The diagnostic capacity of SNHG3 for all cancers in TCGA database was evaluated from the perspective of pooled sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC) of the summary receiver operating characteristic (sROC) curve. Also, this research studied the correlation of SNHG3 expression and the overall survival to access its prognostic value. A sum total of 11,888 cancer patients and 730 controls from 44 eligible studies were enrolled in this integrated analysis. In TCGA database, SNHG3 was significantly upregulated in most types of cancers (16/33, 48%). The pooled sensitivity, specificity, and DOR with 95% CIs was 0.72 (95% CI: 0.60-0.82), 0.87 (95% CI: 0.84-0.90), and 18 (95% CI: 11-30), respectively. Similarly, the AUC of the sROC curve was 0.89 (95% CI: 0.86-0.92), indicating SNHG3 was highly conserved as a diagnosis biomarker. Additionally, SNHG3 overexpression significantly deteriorated the overall survival of cancer patients (pooled HR = 1.28, 95% CI:1.11-1.48; P < 0.05). These findings suggest that the lncRNA SNHG3 could serve as a promising diagnostic and prognostic biomarker.

SNHG1/miR-194-5p/MTFR1 Axis Promotes TGFβ1-Induced EMT, Migration and Invasion of Tongue Squamous Cell Carcinoma Cells.

Tongue squamous cell carcinoma (TSCC) is a common malignancy with aggressive biological behaviors. Mitochondrial fission regulator 1 (MTFR1), is aberrantly expressed in head and neck squamous cell carcinoma (HNSC), but its role in TSCC remains unclear. We aimed to explore the role of MTFR1 in TSCC. The expression of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1), microRNA-194-5p and MTFR1 in TSCC cells was measured by RT-qPCR. Luciferase reporter assay and RNA pull down assay were applied to confirm the binding capacity between miR-194-5p and SNHG1 (or MTFR1). TSCC cell invasion and migration were accessed by Transwell assays. The protein levels of MTFR1 and epithelial-mesenchymal transition (EMT) markers were examined by western blot. MTFR1 had high expression level in TSCC. MTFR1 knockdown inhibited transforming growth factor β1 (TGFβ1)-induced EMT, migration and invasion of TSCC cells in vitro. MiR-194-5p targeted MTFR1 and negatively regulated its expression. In addition, SNHG1 upregulated the expression of MTFR1 by binding with miR-194-5p. Importantly, SNHG1 promoted EMT, invasion and migration of TSCC cells by upregulating MTFR1. SNHG1/miR-194-5p/MTFR1 axis promotes TGFβ1-induced EMT, migration and invasion of cells in TSCC, which could be potential targets for treating TSCC patients.

Exosome-mediated transfer of SNHG7 enhances docetaxel resistance in lung adenocarcinoma.

Long noncoding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) has been widely reported in various cancers, including lung adenocarcinoma (LUAD). However, it is largely unknown whether SNHG7 is involved in docetaxel resistance of LUAD. In the current study, we identified the high expression of SNHG7 in docetaxel-resistant cells. Through functional assays, we determined that silencing of SNHG7 decreased IC50 value of LUAD cells to docetaxel and suppressed proliferation and autophagy in LUAD cells, and reversed M2 polarization in macrophages. Mechanistically, we uncovered that SNHG7 promoted autophagy via recruiting human antigen R (HuR) to stabilize autophagy-related genes autophagy related 5 (ATG5) and autophagy related 12 (ATG12). Moreover, exosomal SNHG7 was transmitted from docetaxel-resistant LUAD cells to parental LUAD cells and thus facilitated docetaxel resistance. Additionally, exosomal SNHG7 activated the phosphatidylinositol 3-kinase (PI3K)/AKT pathway to promote M2 polarization in macrophages via recruiting cullin 4A (CUL4A) to induce ubiquitination and degradation of phosphatase and tensin homolog (PTEN). Taken together, we concluded that exosomal SNHG7 enhances docetaxel resistance of LUAD cells through inducing autophagy and macrophage M2 polarization. All findings in the study suggested that SNHG7 may be a promising target for relieving docetaxel resistance in LUAD.

LncRNA SNHG12 promotes the malignant progression of melanoma by targeting miR-199b.

BackgroundMelanoma is a type of tumor caused by the malignant transformation of melanocytes, and has a high degree of malignancy. Small nucleolar RNA host gene 12 (SNHG12) plays an important role in a variety of cancers, but its role in melanoma and its mechanisms are still unclear. In this study, we measured the expression of SNHG12 and explored the molecular mechanisms involved in melanoma.MethodsWe detected the expression level of SNHG12 in melanoma cell lines, and explored the effect of SNHG12 on the proliferation, migration, and invasion of melanoma cells in vitro. Mechanistic studies explored the regulation of downstream genes by SNHG12.ResultsOverexpression of SNHG12 was found in melanoma cell lines, and SNHG12 promoted the proliferation, migration, and invasion of melanoma cells. MiR-199b is a target gene of SNHG12, which was expressed at low levels in melanoma cell lines, and SNHG12 regulated melanoma cell proliferation, migration, and invasion through miR-199b. We also revealed that SNHG12 promoted the expression of the target genes of miR-199b, namely ETS1, PXN, JAG1, and DDR1.ConclusionsSNHG12 is highly expressed in melanoma, and promotes the expression of ETS1, PXN, JAG1, and DDR1 through targeted regulation of miR-199b, thereby promoting the proliferation, migration, and invasion of melanoma cells.