Long non‐coding RNA SNHG20 promotes the tumorigenesis of oral squamous cell carcinoma via targeting miR‐197/LIN28 axis

Long non‐coding RNA (lncRNA) has been verified to participate in the tumour regulation, including oral squamous cell carcinoma (OSCC). Nevertheless, the role of lncRNA SNHG20 on OSCC still remains elusive. Here, we investigate the physiopathologic functions of lncRNA SNHG20 in OSCC tumorigenesis and explore its potential mechanism. LncRNA SNHG20 was up‐regulated in OSCC tissue compared with adjacent non‐tumour tissue. Meanwhile, SNHG20 was overexpressed in cancer stem‐like cells. In vitro and in vivo, loss‐of‐function experiments showed that lncRNA SNHG20 knockdown inhibited proliferative ability, mammosphere‐forming ability, ALDH1 expression, stem factors (LIN28, Nanog, Oct4, SOX2) and tumour growth. Bioinformatics and luciferase reporter assay revealed that miR‐197 targeted the 3′‐untranslated regions of SNHG20 and LIN28 by complementary binding. Validation experiments confirmed the associated functions of SNHG20/miR‐197/LIN28 axis on OSCC proliferation and stemness. In summary, our results reveal the important function of SNHG20/miR‐197/LIN28 axis in the oncogenesis and stemness of OSCC, suggesting the vital role of SNHG20 in OSCC tumorigenesis.     

LncRNA SNHG1 functions as a ceRNA to antagonize the effect of miR‐145a‐5p on the down‐regulation of NUAK1 in nasopharyngeal carcinoma cell

How lncRNA SNHG1 influences the aggressiveness of nasopharyngeal carcinoma cells as well as the underlying mechanism was studied. The lncRNA differences were analysed by GSE12452 gene microarray. The expression of SNHG1, MiR‐145‐5p and NUAK1 was identified by qRT‐PCR and western blot. Transfection was conducted to construct nasopharyngeal carcinoma cells with different expressions of SNHG1, miR‐145‐5p and NUAK1. Dual‐luciferase reporter assay was performed to explore the relationship between SNHG1, miR‐145‐5p and NUAK1. Wound‐healing assay and transwell invasion experiments were employed to study changes in cell migration capacity and cell invasion, respectively. Tumour xenografts were performed to observe lung metastasis of nude mice inoculated with transfected CNE cells. SNHG1 is highly expressed in nasopharyngeal carcinoma tissues and in cell lines. Down‐regulation of SNHG1 facilitated the expression of miR‐145‐5p and further suppressed the level of NAUK1 in CNE and HNE‐1 cells. Silencing of SNHG1, up‐regulation of miR‐145‐5p and inhibition of NAUK1 by relative transfection all attenuated the aggressiveness of CNE and HNE‐1 cells both in vivo and in vitro. Moreover, the impaired cell migration and invasion by SNHG1 siRNA could be rescued by cotransfection of miR‐145‐5p in CNE and HNE‐1 cells. LncRNA SNHG1 promoted the expression of NUAK1 by down‐regulating miR‐145‐5p and thus promoted the aggressiveness of nasopharyngeal carcinoma cells through AKT signalling pathway and induced epithelial‐mesenchymal transition (EMT).     

LncRNA SNHG17 promotes gastric cancer progression by epigenetically silencing of p15 and p57

Long noncoding RNAs (lncRNA) are attractive biomarkers and therapeutic targets because of their disease- and stage-restricted expression. Small nucleolar RNA host gene 17 (SNHG17) belongs to a large family of noncoding genes hosting small RNAs, with its expression pattern and biological function not clarified in gastric cancer (GC). Thus, we conducted this study to investigate the functional significance and the underlying mechanisms of SNHG17 in GC progression. Our results showed that SNHG17 expression was upregulated in GC tissues and cells, and its high expression was significantly correlated with increased invasion depth, lymphatic metastasis, and advanced TNM stage. The expression of plasma SNHG17 was also found upregulated in patients with GC compared with healthy controls, with a moderate accuracy for diagnosis of GC (area under the receiver operating characteristic curve = 0.748; 95% CI, 0.666–0.830). Gain- and loss-of-function of SNHG17 revealed that SNHG17 promoted GC cell proliferation, cell cycle progression, invasion, and migration and inhibited apoptosis. Mechanistic investigations showed that SNHG17 was associated with polycomb repressive complex 2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors, including p15 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Furthermore, rescue experiments indicated that SNHG17 functioned as an oncogene via activating enhancer of zeste homolog 2 in GC cells. Our study provides a new perspective for SNHG17 acting as a noncoding oncogene in GC tumorigenesis, and it may serve as a novel early diagnostic marker and potential target for the treatment of GC.     

长非编码RNA SNHG18对人胃癌细胞BGC823增殖和凋亡的影响

目的:探究长非编码RNA SNHG18对胃癌细胞增殖和凋亡的影响。方法:采用实时定量PCR(qRT-PCR)技术检测人胃癌组织及癌旁组织和胃癌细胞系中lncRNA SNHG18的表达;采用MTT和克隆形成试验观察转染SNHG18过表达质粒后胃癌细胞BGC823增殖活力的变化;通过流式细胞术检测lncRNA SNHG18对胃癌细胞BGC823凋亡的影响。结果:相较于癌旁组织和胃正常粘膜上皮细胞系GSE-1,胃癌组织及胃癌细胞系中SNHG18的表达水平显著降低(P0.05);胃癌细胞过表达SNHG18增殖活力以及克隆形成的能力均显著降低(P0.05),而细胞凋亡率明显升高(P0.05)。结论:胃癌组织中长非编码RNA SNHG18呈低表达,可促进胃癌细胞增殖并抑制其凋亡,可能在胃癌发生发展过程中发挥重要作用。     

Long non‐coding RNA SNHG16 promotes proliferation and inhibits apoptosis of diffuse large B‐cell lymphoma cells by targeting miR‐497‐5p/PIM1 axis

The aberrant expression and dysfunction of long non‐coding RNAs (lncRNAs) have been identified as critical factors governing the initiation and progression of different human cancers, including diffuse large B‐cell lymphoma (DLBCL). LncRNA small nucleolar RNA host gene 16 (SNHG16) has been recognized as a tumour‐promoting factor in various types of cancer. However, the biological role of SNHG16 and its underlying mechanism are still unknown in DLBCL. Here we disclosed that SNHG16 was overexpressed in DLBCL tissues and the derived cell lines. SNHG16 knockdown significantly suppressed cell proliferation and cell cycle progression, and it induced apoptosis of DLBCL cells in vitro. Furthermore, silencing of SNHG16 markedly repressed in vivo growth of OCI‐LY7 cells. Mechanistically, SNHG16 directly interacted with miR‐497‐5p by acting as a competing endogenous RNA (ceRNA) and inversely regulated the abundance of miR‐497‐5p in DLBCL cells. Moreover, the proto‐oncogene proviral integration site for Moloney murine leukaemia virus 1 (PIM1) was identified as a novel direct target of miR‐497‐5p. SNHG16 overexpression rescued miR‐497‐5p‐induced down‐regulation of PIM1 in DLBCL cells. Importantly, restoration of PIM1 expression reversed SNHG16 knockdown‐induced inhibition of proliferation, G0/G1 phase arrest and apoptosis of OCI‐LY7 cells. Our study suggests that the SNHG16/miR‐497‐5p/PIM1 axis may provide promising therapeutic targets for DLBCL progression.     

Long noncoding RNA ATB participates in the development of renal cell carcinoma by downregulating p53 via binding to DNMT1

Long noncoding RNA (lncRNA) exerts an essential role in the pathological processes of many diseases. Our previous study found that lncRNA ATB was highly expressed in renal cell carcinoma (RCC). Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and migration-related assays were conducted to access the regulatory effects of lncRNA ATB on proliferative and migratory capacities of RCC cells. Flow cytometry was carried out to determine cell cycle and apoptosis influenced by lncRNA ATB. The interaction among lncRNA ATB, DNMT1, and p53 was evaluated through RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and western blot analyses. The results showed that lncRNA ATB knockdown in RCC cell line ACHN inhibited proliferative and migratory capacities and promoted apoptosis. Meanwhile, overexpression of lncRNA ATB in RCC cell line A-498 promoted proliferative and migratory capacities but inhibited apoptosis. RIP and ChIP assays confirmed that lncRNA ATB can bind to DNMT1 and stabilize its expression; meanwhile, it can promote the binding of DNMT1 to p53. Overexpression of p53 partially reversed the proliferative and migratory changes caused by lncRNA ATB. To sum up, our study revealed that high expression of lncRNA ATB could accelerate the proliferative and migratory rates of RCC cells and inhibit cell apoptosis through downregulating p53 via binding to DNMT1.     

LncRNA SNHG20 contributes to cell proliferation and invasion by upregulating ZFX expression sponging miR-495-3p in gastric cancer

Long noncoding RNAs (lncRNAs) exert key regulators in cancer development and progression. The functional significance of lncRNA small nucleolar RNA host gene 20 (SNHG20) was reported in gastric cancer (GC); however, the underlying molecular mechanism in GC development is largely unknown. Here, our results showed that the lncRNA SNHG20 expression was significantly higher in GC tissues compared with adjacent normal tissues by quantitative real-time PCR (qRT-PCR) analysis. Higher lncRNA SNHG20 expression was highly associated with tumor size and lymphatic metastasis of patients. Patients with higher lncRNA SNHG20 expression predicted a short disease-free survival (DFS) and overall survival (OS). Furthermore, lncRNA SNHG20 expression negatively associated with miR-495-3p expression and regulated miR-495-3p expression. Function assays confirmed that lncRNA SNHG20 knockdown using RNA interference suppressed cell proliferation and invasion of GC by negatively regulating miR-495-3p expression. Moreover, we demonstrated that lncRNA SNHG20 inhibited zinc finger protein X-linked (ZFX) expression by negatively miR-495-3p expression in GC cells. In vivo, the current study also indicated that lncRNA SNHG20 knockdown reduced the tumor growth by downregulating ZFX expression. Thus, our results implied that inhibition of SNHG20/miR-495-3p/ZFX axis may provide valuable target for GC treatment.     

The lncRNA SNHG16 affects prognosis in hepatocellular carcinoma by regulating p62 expression

Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.     

LncRNA SNHG14/miR-497a-5p/BACE1 axis modulates obesity-induced adipocyte inflammation and endoplasmic reticulum stress

Obesity is a metabolic disease with excess weight. LncRNA SNHG14 is abnormally expressed in numerous diseases. This research aimed to enucleate the lncRNA SNHG14 role in obesity. Adipocytes were treated with free fatty acid (FFA) to establish an in vitro model for obesity. Mice were fed a high-fat diet to construct an in vivo model. Gene levels were determined using quantitative real-time PCR (RT-PCR). The protein level was checked by western blot. The lncRNA SNHG14 role in obesity was assessed using western blot and enzyme-linked immunosorbent assay. The mechanism was estimated by Starbase, dual-luciferase reporter gene assay, and RNA pull-down. LncRNA SNHG14 function in obesity was estimated using mouse xenograft models, RT-PCR, western blot, and enzyme-linked immunosorbent assay. LncRNA SNHG14 and BACE1 levels were increased, but the miR-497a-5p level was decreased in FFA-induced adipocytes. Interference with lncRNA SNHG14 reduced endoplasmic reticulum (ER) stress-related molecules GRP78 and CHOP expressions in FFA-induced adipocytes, and decreased IL-1β, IL-6, and TNF-α expressions, indicating that lncRNA SNHG14 knockdown mitigated FFA-induced ER stress and inflammation in adipocytes. Mechanistically, lncRNA SNHG14 combined with miR-497a-5p, and miR-497a-5p targeted BACE1. Meanwhile, lncRNA SNHG14 knockdown reduced levels of GRP78, CHOP, IL-1β, IL-6, and TNF-α, while cotransfection with anti-miR-497a-5p or pcDNA-BACE1 abolished these trends. Rescue assays illustrated that lncRNA SNHG14 knockdown relieved FFA-induced adipocyte ER stress and inflammation through miR-497a-5p/BACE1. Meanwhile, lncRNA SNHG14 knockdown restrained adipose inflammation and ER stress caused by obesity in vivo. LncRNA SNHG14 mediated obesity-induced adipose inflammation and ER stress through miR-497a-5p/BACE1.     

Serum withdrawal up‐regulates human SIRT1 gene expression in a p53‐dependent manner

SIRT1, a nicotinamide adenine dinucleotide (NAD⁺)‐dependent histone/protein deacetylase, has been extensively studied recently for its critical role in the regulation of physiology, calorie restriction and aging. Studies on laboratory mice showed that expression of SIRT1 can be induced by starvation in a p53‐dependent manner and requires the p53‐binding sites present in the Sirt1 promoter. However, it remains to be determined whether these findings based on rodents apply to human beings. In this paper, we characterized a putative p53‐binding element in the human SIRT1 promoter that might be required for the up‐regulation of SIRT1 in response to nutritional stress. The p53‐binding site in the promoter of human SIRT1 is more deviant from the consensus sequence than the corresponding sequence in the mouse Sirt1. There is a C to A change at the second half site in human SIRT1, thus disrupting the core‐binding element CWWG in the canonical RRRCWWGYYY. To test whether such sequence change would affect its binding with p53 and the SIRT1 expression under stress, we studied various human cell lines with different p53 status and cells with ectopic expression of functionally distinct p53. We found that serum withdrawal also up‐regulates human SIRT1 gene expression in a p53‐dependent manner and that the p53‐binding element in SIRT1 is required for the up‐regulation. Thus, the mechanism responsible for the regulation of SIRT1 expression by p53 is conserved between mice and human beings.     

The lncRNA SNHG15/miR-18a-5p axis promotes cell proliferation in ovarian cancer through activating Akt/mTOR signaling pathway

Here, we report the expression pattern, function and regulatory mechanism of SNHG15 together with miR-18a-5p micro RNA in ovarian cancer (OC) for the first time. We recruited 20 patients and took normal ovarian tissues and ovarian tumor tissues from them. We used cell culture, transfection, in vivo tumor xenograft assay, and multiple types of detection assays to investigate the expression and regulation of long noncoding RNA (lncRNA) SNHG15/miR-18a-5p in ovarian tissues and cells. Results: We found that the messenger RNA expression level of SNHG15 was significantly higher and miR-18 was decreased in ovarian cancer tissues and in OC cells. Functional experiments showed that SNHG15 overexpression potentiated the migration and invasion of OC cells, while SNHG15 inhibition reduced the tumor proliferation, which was restored via overexpression of miR-18a. SNHG15 was found to directly target and suppress the expression of miR-18a. Our results illustrate the possible molecular mechanism of lncRNA SNHG15/miR-18a-5p functions in cell proliferation in OC. SNHG15/miR-18a promoted the progression of OC cells via the protein kinase B/mammalian target of rapamycin signaling pathway.