lncRNA SNHG1 Research Articles

Long noncoding RNA SNHG1 promotes human prostate cancer progression by sponging miR-383-5p.

Prostate cancer is the most common urinary malignancy in males. Long noncoding RNA small nucleolar RNA host gene 1 (lncRNA SNHG1) has been reported to play a crucial role in the development of various cancers. However, the understanding of SNHG1 in prostate cancer is still limited and needs further investigation. In this study, we found the level of SNHG1 was significantly upregulated in prostate cancer tissues and cells. Knockdown of SNHG1 significantly suppressed proliferation, migration and invasion and promoted cell apoptosis in prostate cancer cells. In addition, knockdown of SNHG1 significantly downregulated proliferating cell nuclear antigen and upregulated cleaved caspase-3. MiR-383-5p was identified to be a target of SNHG1 by bioinformatics analysis, dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. MiR-383-5p was significantly downregulated in prostate cancer tissues and cells. Inhibition of miR-383-5p could partially restore the effects of SNHG1 knockdown on prostate cancer cell proliferation, apoptosis, migration and invasion. Furthermore, murine xenograft models were established to investigate the effects of SNHG1 and miR-383-5p in tumorigenesis in vivo. We found SNHG1 knockdown or miR-383-5p overexpression repressed tumor growth in vivo. In conclusion, SNHG1 contributed to prostate cancer progression by targeting miR-383-5p, elucidating that SNHG1 might be a target for prostate cancer therapy.

LncRNA SNHG16 contributes to tumor progression via the miR-302b-3p/SLC2A4 axis in pancreatic adenocarcinoma

BackgroundIt has been reported that the lncRNA SNHG16 has significantly increased expression in pancreatic adenocarcinoma (PC). However, the functions and mechanisms of SNHG16 are not clear. The aim of this study was to explore the effects of SNHG16 on PC.MethodsqRT-PCR analysis was applied to detect the expression levels of SNHG16, miR-302b-3p and SLC2A4 in PC tissues and cells. CCK8 and EdU assays were used to evaluate the proliferation of PC cells. Transwell assays were used to assess PC cell migration and invasion. Apoptosis was evaluated by flow cytometry, and the expression of apoptosis-related proteins (including Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9) was tested by western blotting. The interactions between miR-302b-3p and SNHG16 or miR-302b-3p and the 3’UTR of SLC2A4 mRNA were clarified by a dual luciferase reporter assay and RNA immunoprecipitation.ResultsSNHG16 expression was significantly elevated in PC tissues and cell lines and was associated with poor prognosis of PC patients. Knockdown of SNHG16 reduced PC cell proliferation, migration and invasion. SNHG16 acted as a sponge to regulate miR-302b-3p expression in PC cells. In addition, miR-302b-3p targeted SLC2A4 directly.ConclusionsSNHG16 promoted the progression of PC via the miR-302b-3p/SLC2A4 axis and was expected to be a potential target for the early diagnosis and treatment of PC.

Silence of Long Noncoding RNA SNHG14 Alleviates Ischemia/Reperfusion-Induced Acute Kidney Injury by Regulating miR-124-3p/MMP2 Axis.

Purpose Ample evidence has proved that lncRNAs are pivotal regulators in acute kidney injury (AKI). Here, we focus on the role and mechanism of lncRNA SNHG14 in ischemia/reperfusion- (I/R-) caused AKI. Methods I/R and hypoxia/reoxygenation (H/R) were applied to induce rats and HK-2 cells to establish AKI models in vivo and in vitro. Relative expression of SNHG14, miR-124-3p, and MMP2 was determined by qRT-PCR. HE staining was used to evaluate pathological changes in renal tissues, and acute tubular necrosis (ATN) score was calculated. Renal function was evaluated by measuring serum creatinine content and blood urea nitrogen content. Levels of IL-1β, IL-6, and TNF-α were measured by ELISA. Cell viability was examined by MTT assay. Oxidative stress was assessed by measuring SOD, MDA, and ROS levels. The target of SNHG14 or miR-124-3p was verified by DLR assay. Protein expression of MMP2 was examined by western blot. Results SNHG14 was boosted in renal tissues of I/R-stimulated rats and H/R-induced HK-2 cells, while miR-124-3p was diminished in H/R-stimulated HK-2 cells. Si-SNHG14 or miR-124-3p mimics repressed inflammation and oxidative stress and enhanced cell viability in H/R-stimulated HK-2 cells. Sh-SNHG14 mitigated I/R-induced AKI in rats. MiR-124-3p was targeted by SNHG14, and MMP2 was targeted by miR-124-3p. Inhibition of miR-124-3p or upregulation of MMP2 reversed inhibitory effects of SNHG14 silence on inflammation and oxidative stress as well as the promoting effect of SNHG14 silence on cell viability in H/R-induced HK-2 cells. Conclusion Knockdown of SNHG14 alleviated I/R-induced AKI by miR-124-3p-mediated downregulation of MMP2.

Long noncoding RNA SNHG20 regulates cell migration, invasion, and proliferation via the microRNA-19b-3p/RAB14 axis in oral squamous cell carcinoma

ABSTRACT Oral squamous cell carcinoma (OSCC) is one of the most common digestive tumors, which has high mortality rate. Long non-coding RNAs (lncRNA) and MicroRNAs (miRNAs) are associated with the cell cycle and differentiation during the occurrence and development of malignant tumors. This research aimed to investigate the effects of lncRNA SNHG20 on the progress of oral squamous cell carcinoma (OSCC) cells. Ninety pairs of tumor tissues and paracancerous tissues were collected from patients with OSCC and the CAL27 and SCC25 OSCC cells were selected for the following experiments. RT-qPCR was used for detecting the expression of SNHG20, miR-19b-3p, and RAB14. Western blotting was used to detect the protein levels of RAB14. MTT assay was employed to assess cell proliferation. Transwell assay was used to determine the cell migration and invasion abilities. Furthermore, luciferase reporter and RNA pull-down assays were used to verify the binding of SNHG20/RAB14 to miR-19b-3p. Then, the function of the SNHG20/miR-19b-3p/RAB14 axis in OSCC was explored. The results indicated that lncRNA SNHG20 was upregulated in the tissues. Furthermore, bioinformatic analysis showed that both SNHG20 and RAB14 could bind to miR-19b-3p. RAB14 was upregulated, and miR-19b-3p was downregulated in the tissues. The knockdown of SNHG20 inhibited cell proliferation, migration, and invasion. Contrarily, the knockdown of miR-19b-3p reversed the effects of si-SNHG20 on cell proliferation, migration, and invasion, and the overexpression of RAB14 reversed the effects of miR-19b-3p mimic on the cell biological functions. LncRNA SNHG20 affects cell proliferation, migration, and invasion via the miR-19b-3p/RAB14 axis in OSCC.

LncRNA SNHG14 promotes cell proliferation and invasion in colorectal cancer through modulating miR-519b-3p/DDX5 axis.

Numbers of studies suggest that long non-coding RNAs (lncRNAs) exert an important role in cancer progression. It is reported that lncRNA SNHG14 (SNHG14) promotes cell proliferation and invasion in many cancers. However, the underlying molecular mechanism of SNHG14 in colorectal cancer (CRC) remains unclear. In our study, we found that SNHG14 is highly expressed in CRC tissues and cells, especially in SW480 and HT-29 cells. In addition, sh-SNHG14 inhibits cell proliferation, cell migration and invasion, promotes cell apoptosis in CRC cell lines. Furthermore, we found that SNHG14 functions as a sponge for miR-519b-3p, while the DEAD box protein 5 (DDX5) is a downstream target gene of miR-519b-3p, and the functions of miR-519b-3p inhibitors on the CRC progression could be rescued by downregulation of DDX5. Our findings suggest that SNHG14 promotes the CRC progression by miR-519b-3p/DDX5 axis, implying the promising therapeutic target of SNHG4 for CRC patients.

Long non-coding RNA SNHG5 regulates ulcerative colitis via microRNA-375 / Janus kinase-2 axis

ABSTRACT Ulcerative colitis (UC) is an intestinal inflammatory disorder. Long non-coding RNAs (lncRNAs) are collectively involved in UC. This study is designed to explore the roles of lncRNA (small nucleolar RNA host gene 5) SNHG5 in UC. Gene or microRNA (miRNA) expression was detected using RT-qPCR and western blot, respectively. Cellular functions were analyzed by cell counting kit 8 (CCK8), 5-ethynyl-2′-deoxyuridine (EdU) assay, flow cytometry, and the terminal deoxyribonucleotidyl transferase (TDT)‐mediated dUTP‐digoxigenin nick end labeling (TUNEL) assays. Lactate dehydrogenase (LDH) content was determined by a cell cytotoxicity assay. The interactions between miR-375 and SNHG5 or Janus kinase-2 (JAK2) were verified by a luciferase reporter assay. SNHG5 was up-regulated in intestinal mucosa tissues of UC patients as well as tumor necrosis factor alpha-treated (TNF-α-treated) young adult mouse colon (YAMC) cells. Down-regulated SNHG5 promoted cell proliferation and inhibited apoptosis of YAMC cells. miR-375 was verified to be a target of SNHG5 and was suppressed by TNF-α treatment in YAMC cells. Over-expression of miR-375 restored YAMC cellular functions. Additionally, miR-375 targeted JAK2, which was up-regulated by TNF-α treated YAMC cells. Up-regulation of JAK2 induced the dysfunction of YAMC cells. Knockdown of SNHG5 promoted the proliferation and suppressed the apoptosis of YAMC cells via regulating miR-375/JAK2 axis. Therefore, knockdown of SNHG5 may be a promising therapy for UC.

Mechanism of Autonomic Exercise Improving Cognitive Function of Alzheimer's Disease by Regulating lncRNA SNHG14.

This paper studied the influence of exercise on the cognitive ability of AD patients and elucidated potential mechanisms. The expression of SNHG14 was validated by qRT-PCR. The cognitive impairment of mice was examined by MWM Test. ELISA tests were applied to discover the influence of SNHG14 on inflammation. Overexpression of SNHG14 was found in AD patients and underexpression of SNHG14 was identified in these AD patients after exercise. In APP/PS1 double transgenic mice, SNHG14 reversed the protective impacts of exercise on escape latency and distance moved. The upregulation of SNHG14 also inhibited the effects of exercise on the percentage of time spent in the target quadrant and times of platform crossing. Besides, overexpression of SNHG14 reversed the repressed expression of IL-6, IL-1β, and TNF-α. In total, exercise could ameliorate cognitive disorder and inflammation activity by reducing the levels of SNHG14.

Retraction: LncRNA SNHG5 regulates the cell viability and apoptosis of glioma cells by the miR-1297/KPNA2 axis.

Retraction of ‘LncRNA SNHG5 regulates the cell viability and apoptosis of glioma cells by the miR-1297/KPNA2 axis’ by Xueyuan Li et al., RSC Adv., 2020, 10, 1498–1506, DOI: 10.1039/C9RA08693E

LncRNA SNHG1 promotes the development of oral cavity cancer via regulating the miR-421/HMGB2 axis

Oral cancer (OC) is a common malignant tumor in oral surgery, which is prone to metastasis and the prognosis is not optimistic. Long-non-coding RNA (lncRNA) is a kind of endogenous transcripts with more than 200bp in length, lack of specific and complete open reading frame, and does not have the function of protein-coding. Studies have found that it can regulate gene expression at many levels, such as epigenetic level, transcriptional level and post-transcriptional level, thus affecting the occurrence and development of diseases. Recent studies have shown that the occurrence, development, of oral cancer, are associated with lncRNA. In this research, we found that lncRNA SNHG1 was up-regulated in oral cancer. Knockdown of lncRNA SNHG1 would inhibit the proliferation of oral cancer cells. Then we revealed a new mechanism that lncRNA SNHG1 regulated the growth of oral cancer via controlling the miR-421/HMGB2 axis, which provided new therapy for patients with oral cancer.

RETRACTED: The effect of LncRNA SNHG16 on vascular smooth muscle cells in CHD by targeting miRNA-218-5p

To explore the role of SNHG16 in coronary heart disease (CHD) and its effect on vascular smooth muscle cells via miR-218-5p. A quantitative real time polymerase chain reaction (qRT-PCR) assay was carried out to determine the expression of serum SNHG16 and miR-218-5p in the observation group before and after treatment and in the control group. Then, receiver operating characteristic (ROC) curves were drawn to analyze the value of SNHG16 and miR-218-5p in the diagnosis and prognosis prediction of CHD. Furthermore, purchased coronary artery smooth muscle cells (HCASMC) were transfected with SNHG16 mimics, SNHG16 inhibitor, miR-218-5p mimics, miR-218-5p inhibitor, or negative control, and then the cell proliferation, migration, apoptosis, and apoptosis-related proteins (Bax, Bcl-2, and Caspase-3) and Wnt/β-catenin signaling pathway-related proteins (c-myc and β-catenin) in the cells were detected. Both SNHG16 and miR-218-5 had good predictive value for the development and recurrence of CHD (P<0.001). In addition, cell experiments showed that inhibition of SNHG16 weakened the proliferation and migration of HCASMC cells and intensified their apoptosis, SNHG16 and miR-218-5p had the same binding sites, and the dual luciferase reporter assay revealed that the fluorescence activity of HG16-WT was inhibited by transfected miR-mimics, but enhanced by transfected miR-inhibitor (both P<0.050). Furthermore, the rescue experiment revealed that the effect of inhibiting SNHG16 on HCASMC cells was completely reversed by miR-218-5p (P>0.050). Highly expressed SNHG16 targetedly regulates miR-218-5p and promotes the proliferation and migration of HCASMC via the Wnt/β-catenin signaling pathway, giving rise to CHD.

Long non-coding RNA SNHG20 promotes ovarian cancer development by targeting microRNA-338-3p to regulate MCL1 expression.

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs) were reported to be associated with the development of ovarian cancer (OC). Increasing evidence demonstrated that lncRNA SNHG20 and miR-338-3p were involved in OC. However, the functional mechanism of lncRNA SNHG20 and miR-338-3p in OC development remains unknown. The expression of SNHG20, miR-338-3p and myeloid cell leukemia 1 (MCL1) was detected by reverse transcription-quantitative PCR. MTT assay, flow cytometry and transwell migration and invasion assays were used to assess cell proliferation, apoptosis, migration and invasion, respectively. The relative protein expression was detected by western blot analysis. The interaction between miR-338-3p and SNHG20 or MCL1 was predicted by starBase v3.0, and subsequently confirmed by dual-luciferase reporter assay. Besides, mouse xenograft assay was carried out to explore the effect of SNHG20 on tumor growth in vivo. The levels of SNHG20 and MCL1 were upregulated, while miR-338-3p level was downregulated in OC tissues and cells. SNHG20 knockdown repressed OC cell proliferation, migration, invasion and epithelial-mesenchymal transition, and induced apoptosis. Interestingly, SNHG20 targeted miR-338-3p to regulate MCL1 expression. miR-338-3p depletion or MCL1 overexpression could reverse the effects of SNHG20 knockdown on OC cells. Besides, SNHG20 knockdown impeded tumor growth in vivo. In conclusion, the present study demonstrated that SNHG20 regulates OC development via modulation of the miR-338-3p/MCL1 axis, providing the theoretical basis for the treatment of OC.

LncRNA SNHG7 alleviates IL-1β-induced osteoarthritis by inhibiting miR-214-5p-mediated PPARGC1B signaling pathways

BackgroundAs a common joint disease, osteoarthritis (OA) is the main cause of limited joint mobility and disability. The role of lncRNAs in the regulation of OA is increasingly discovered. Therefore, further exploring the function of SNHG7 in OA is of great significance for understanding its occurrence and development. MethodsWe used interleukin-1β (IL-1β) to treat to establish an OA model primary on chondrocytes in vitro, and gain- and loss of function assays of SNHG7 and miR-214-5p were conducted. The cell viability and apoptosis of chondrocytes were detected by CCK8 assay, BrdU assay and flow cytometry. The inflammatory cytokines (IL-1β, IL-6 and TNF-α), NLRP3 inflammasome, protein level of PPARGC1B, PPARγ, P38 and NF-κB were determined by RT-PCR and/or western blot. ResultsThe results showed that SNHG7 was distinctly downregulated, while miR-214-5p was significantly upregulated in OA patients and primary chondrocytes treated with IL-1β. In addition, SNHG7 enhanced cell viability, inhibited apoptosis and inflammation of IL-1β-mediated chondrocytes. In contrast, miR-214-5p upregulation reduced viability, promoted apoptosis and inflammation of chondrocytes. Mechanistically, SNHG7 served as a competitive endogenous RNA by sponging miR-214-5p, which targeted PPARGC1B. Besides, the results of the compensation experiment affirmed that miR-214-5p attenuates SNHG7-mediated protective effects on IL-1β-mediated chondrocytes against apoptosis and inflammation, and activating PPARγ pathway markedly dampened the cytotoxic effects of miR-214-5p. ConclusionsCollectively, The above results confirmed that SNHG7 prevents IL-1β induced OA by inhibiting NLRP3 inflammasome and apoptosis through miR-214-5p/PPARGC1B axis.

LncRNA SNHG16 Regulates the Progress of Acute Myeloid Leukemia Through miR183-5p-FOXO1 Axis.

PurposeAt present, there is a lack of precise knowledge on acute myeloid leukemia (AML) at the molecular level, and understanding its occurrence at the genetic level is conducive to the development of targeted therapies. Therefore, in this study the relationship between the lncRNA SNHG1 –miR183-5p–FOXO1 axis and AML was explored.MethodsExpression of lncRNA SNHG16 and miR183-5p was quantified by quantitative real-time PCR, and the level of FOXO1 and other proteins was measured by Western blot. Expression vectors of lncRNA SNHG16, miR183-5p, and FOXO1 were constructed to assess effects of the three on cell proliferation and apoptosis. MTT reduction assays were employed for cell proliferation, flow cytometry for cell cycle and apoptosis, and dual luciferase–reporter assays for the targeting relationship between lncRNA SNHG16 and miR183-5p and miR183-5p and FOXO1.ResultslncRNA SNHG16 was highly expressed in peripheral blood/leukemia cell lines of patients with AML compared with normal human peripheral blood/peripheral blood mononuclear cells. miR183-5p was the target of lncRNA SNHG16 and FOXO1 the target gene of miR183-5p rather than lncRNA SNHG16. Absence of lncRNA SNHG16 led to upregulation of miR183-5p, promotion of apoptosis, and inhibition of proliferation. Suppression of miR183-5p accelerated cell proliferation and hindered apoptosis. miR183-5p negatively regulated FOXO1, and FOXO1 promoted proliferation and inhibited apoptosis. Inhibition of miR183-5p counteracted the changes caused by lncRNA SNHG16 absence.ConclusionlncRNA SNHG16 regulates the progress of AML via the miR183-5p–FOXO1 axis.

LncRNA SNHG1 attenuates neuropathic pain following spinal cord injury by regulating CDK4 level.

Neuropathic pain (NP) is one of the most intractable complications of spinal cord injury (SCI). This study aims to explore the role of long non-coding RNA (lncRNA) SNHG1 in influencing SCI-induced NP. After establishment of the spinal nerve ligation (SNL) model in rats, spinal tissues were extracted. SNHG1 level in rat spinal tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The role of SNHG1 in the development of NP was explored by assessing paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in model rats. The interaction between SNHG1 and CDK4 was explored by Luciferase assay and RIP (RNA-Binding Protein Immunoprecipitation). Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were conducted to determine inflammatory factor levels in rat spinal tissues. SNHG1 was upregulated in rats undergoing SNL. Knockdown of SNHG1 alleviated the development of NP and overexpression of SNHG1 was capable of inducing NP symptoms in uninjured rats. SNHG1 induced NP by directly regulating CDK4 level. SNHG1 is a novel target in the treatment of NP associated with neuroinflammation.

Knockdown of Long Noncoding RNA SNHG14 Protects H9c2 Cells Against Hypoxia-induced Injury by Modulating miR-25-3p/KLF4 Axis in Vitro.

Cyanotic congenital heart disease (CCHD) is the main cause of death in infants worldwide. Long noncoding RNAs (lncRNAs) have been pointed to exert crucial roles in development of CHD. The current research is designed to illuminate the impact and potential mechanism of lncRNA SNHG14 in CCHD in vitro. The embryonic rat ventricular myocardial cells (H9c2 cells) were exposed to hypoxia to establish the model of CCHD in vitro. Quantitative real-time polymerase chain reaction was conducted to examine relative expressions of SNHG14, miR-25-3p, and KLF4. Cell viability was determined by the MTT assay. Lactate dehydrogenase (LDH) was measured by an LDH assay kit. Apoptosis-related proteins (Bax and Bcl-2) and KLF4 were detected by Western Blot. The targets of SNHG14 and miR-25-3p were verified by the dual-luciferase reporter assay. SNHG14 and KLF4 were upregulated, whereas miR-25-3p was downregulated in hypoxia-induced H9c2 cells and cardiac tissues of patients with CCHD compared with their controls. Knockdown of SNHG14 or overexpression of miR-25-3p facilitated cell viability, while depressing cell apoptosis and release of LDH in hypoxia-induced H9c2 cells. MiR-25-3p was a target of SNHG14 and inversely modulated by SNHG14. MiR-25-3p could directly target KLF4 and negatively regulate expression of KLF4. Repression of miR-25-3p or overexpression of KLF4 reversed the suppression impacts of sh-SNHG14 on cell apoptosis and release of LDH as well as the promotion impact of sh-SNHG14 on cell viability in hypoxia-induced H9c2 cells. Sh-SNHG14 protected H9c2 cells against hypoxia-induced injury by modulating miR-25-3p/KLF4 axis in vitro.

Correlation between lncRNA SNHG16 gene polymorphism and its interaction with environmental factors and susceptibility to colorectal cancer.

Objective:To study the relationship between long-chain non-coding RNA small nucleolar RNA host gene 16 (lncRNA SNHG16) polymorphisms and its interaction with environmental factors and susceptibility to colorectal cancer (CRC).Methods:Sanger sequencing was used to analyze genotypes of lncRNA SNHG16 gene rs7353, rs8038, and rs15278 sites. Multifactor dimensionality reduction was used to analyze interactions between lncRNA SNHG16 gene rs7353, rs8038, rs15278 sites, and environmental factors. Haploview 4.1 software was used to analyze linkage disequilibrium of lncRNA SNHG16 gene rs7353, rs8038, and rs15278 sites. Quantitative real-time polymerase chain reaction was used to analyze plasma lncRNA SNHG16 levels of CRC patients and control subjects.Results:Variation of the lncRNA SNHG16 gene rs7353 site A>G variation was associated with decreased CRC susceptibility (Odds ratio [OR] = 0.50, 95% confidence interval [CI]: 0.40–0.62, P < .01). The rs8038 site G>A and rs15278 site A>G variation were associated with increased CRC susceptibility (OR = 1.87, 95% CI: 1.47–2.36, P < .01). The rs15278 site G>A variation was associated with increased CRC susceptibility (OR = 2.24, 95% CI: 1.61–3.11, P < .01). Interaction combinations featuring age, rs7353, rs8038, and rs15278 single nucleotide polymorphism are 13.53 times more susceptible to CRC than other interactions (95% CI: 9.43–19.41, P < .01). The rs15278, rs8038, and rs7353 site AGA haplotypes were significantly associated with a decreased CRC risk (OR = 0.65, 95% CI: 0.48–0.88, P = .01), AAG haplotypes were significantly associated with an increased CRC risk (OR = 2.00, 95% CI: 1.27–3.17, P < .01). High lncRNA SNHG16 expression was associated with tumor progression in CRC patients (χ2 = 8.85, P = .03). The rs7353 site A>G variation caused a significant decrease in plasma lncRNA SNHG16 level (P < .01), while the rs8038 site G>A variation and rs15278 site A>G variation resulted in increased plasma lncRNA SNHG16 levels.Conclusion:Polymorphisms of lncRNA SNHG16 gene rs7353, rs8038, rs15278 loci and their interaction with age are significantly associated with CRC susceptibility.

LncRNA SNHG7 Mediates the Chemoresistance and Stemness of Breast Cancer by Sponging miR-34a.

Chemoresistance is considered to be a major cause of the recurrence and metastasis of breast cancer (BC). LncRNA SNHG7 has been reported to be upregulated in breast cancer and to promote tumor progression and metastasis. Nevertheless, the function and potential regulatory mechanism of SNHG7 in BC drug resistance are still largely unclear. This study indicated that SNHG7 was highly expressed in chemoresistant BC tissues and cells. Upregulated SNHG7 might predict a low pCR rate and poor clinical outcome in BC patients. Knockdown of SNHG7 enhanced drug sensitivity and drug-induced apoptosis in chemoresistant BC cells. In terms of the mechanism, miR-34a was found to be a target of SNHG7 and its expression in breast cancer tissues and chemoresistant cell lines was negatively correlated with SNHG7 expression. Importantly, sh-SNHG7 upregulated miR-34a expression, reduced the percentages of CD44+/CD24−cells, and inhibited sphere-formation and stem cell factor (Oct4, Nanog, SOX2) expression. Functional loss experiments showed that the repressive effect of SNHG7 knockdown on BC cell stemness was partially reversed by transfection with miR-34a inhibitors. In summary, this study indicated that SNHG7 contributed to the chemoresistance of BC and mediated chemoresistance and cancer stemness by sponging miR-34a.

LncRNA SNHG3 accelerates the proliferation and invasion of non-small cell lung cancer by downregulating miR-340-5p.

Small nucleolar RNA host genes (SNHGs) as a subset of long non-coding RNAs (lncRNAs) act critical roles in tumor progression. The present study aimed to elucidate the role and mechanisms of SNHG3 in non-small cell lung cancer (NSCLC). The correlation of SNHG3/miR-340-5p/HOXA10 with the clinicopathological features and outcomes in NSCLC was analyzed by TCGA cohort. In vitro and in vivo functional experiments were conducted to assess the role of SNHG3 in NSCLC cells. Bioinformatic analysis and luciferase gene reporter were used to estimate the interaction between miR-340-5p and SNHG3/HOXA10 3'UTR. The effects of SNHG3 and (or) miR-340-5p on HOXA10 expression were detected by qRT-PCR and Western blot analysis. As a consequence, the elevated expression of SNHG3 and HOXA10 or lowered expression of miR-340-5p was related to the lymph node infiltration, distant metastases and unfavorable prognosis in NSCLC. Ectopic expression of SNHG3 boosted the proliferation and invasion of NSCLC cells in vitro and in vivo, whereas downregulation of SNHG3 reversed these effects. Moreover, SNHG3 could bind with miR-340-5p and reduce its expression levels, and miR-340-5p attenuated SNHG3-induced tumor proliferation and HOXA10 expression in NSCLC cells. Our findings unveiled that SNHG3 might be an oncogenic factor in NSCLC by downregulating miR-340-5p.

Identification of biomarkers and pathways in hypertensive nephropathy based on the ceRNA regulatory network

BackgroundHypertensive nephropathy (HTN) is a kind of renal injury caused by chronic hypertension, which seriously affect people’s life. The purpose of this study was to identify the potential biomarkers of HTN and understand its possible mechanisms.MethodsThe dataset numbered GSE28260 related to hypertensive and normotensive was downloaded from NCBI Gene Expression Omnibus. Then, the differentially expressed RNAs (DERs) were screened using R limma package, and functional analyses of DE-mRNA were performed by DAVID. Afterwards, a ceRNA network was established and KEGG pathway was analyzed based on the Gene Set Enrichment Analysis (GSEA) database. Finally, a ceRNA regulatory network directly associated with HTN was proposed.ResultsA total of 947 DERs were identified, including 900 DE-mRNAs, 20 DE-lncRNAs and 27 DE-miRNAs. Based on these DE-mRNAs, they were involved in biological processes such as fatty acid beta-oxidation, IRE1-mediated unfolded protein response, and transmembrane transport, and many KEGG pathways like glycine, serine and threonine metabolism, carbon metabolism. Subsequently, lncRNAs KCTD21-AS1, LINC00470 and SNHG14 were found to be hub nodes in the ceRNA regulatory network. KEGG analysis showed that insulin signaling pathway, glycine, serine and threonine metabolism, pathways in cancer, lysosome, and apoptosis was associated with hypertensive. Finally, insulin signaling pathway was screened to directly associate with HTN and was regulated by mRNAs PPP1R3C, PPKAR2B and AKT3, miRNA has-miR-107, and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG.ConclusionsInsulin signaling pathway was directly associated with HTN, and miRNA has-miR-107 and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG were the biomarkers of HTN. These results would improve our understanding of the occurrence and development of HTN.

Si-SNHG5-FOXF2 inhibits TGF-\u03b21-induced fibrosis in human primary endometrial stromal cells by the Wnt/\u03b2-catenin signalling pathway

BackgroundIntrauterine adhesions (IUAs) are manifestations of endometrial fibrosis characterized by inflammation and fibrinogen aggregation in the extracellular matrix (ECM). The available therapeutic interventions for IUA are insufficiently effective in the clinical setting for postoperative adhesion recurrence and infertility problems. In this study, we investigated whether si-SNHG5-FOXF2 can serve as a molecular mechanism for the inhibition of IUA fibrosis ex vivo.MethodsFOXF2, TGF-β1 and collagen expression levels were measured by microarray sequencing analysis in three normal endometrium groups and six IUA patients. We induced primary human endometrial stromal cells (HESCs) into myofibroblasts (MFs) to develop an IUA cell model with various concentrations of TGF-β1 at various times. Downstream target genes of FOXF2 were screened by chromatin immunoprecipitation combined with whole-genome high-throughput sequencing (ChIP-seq). We investigated ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related proteins in primary HESCs with FOXF2 downregulation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting (WB), immunohistochemistry (IHC), flow cytometry, ethylenediurea (EdU) and CCK8 assays. We identified long noncoding RNAs (lncRNA) SNHG5 as the upstream regulatory gene of FOXF2 through RNA immunoprecipitation (RIP), RNA pulldown and fluorescence in situ hybridization (FISH). Finally, we examined FOXF2 expression, ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related proteins in primary HESCs upon FOXF2 downregulation.ResultsFOXF2 was highly expressed in the endometrium of patients with IUA. Treatment of primary HESCs with 10 ng/ml TGF-β1 for 72 h was found to be most effective for developing an IUA cell model. FOXF2 regulated multiple downstream target genes, including collagen, vimentin (VIM) and cyclin D2/DK4, by ChIP-seq and ChIP-PCR. FOXF2 downregulation inhibited TGF-β1-mediated primary HESC fibrosis, including ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related protein expression. We identified lncRNA SNHG5 as an upstream gene that directly regulates FOXF2 by RIP-seq, qRT-PCR, WB and FISH. SNHG5 downregulation suppressed FOXF2 expression in the IUA cell model, resulting in synergistic repression of the Wnt/β-catenin pathway, thereby altering TGF-β1-mediated ECM aggregation in endometrial stromal cells ex vivo.ConclusionsRegulation of the Wnt/β-catenin signalling pathway and ECM formation by si-SNHG5-FOXF2 effectively inhibited the profibrotic effect of TGF-β1 on primary HESCs. This finding can provide a molecular basis for antagonizing TGF-β1-mediated fibrosis in primary HESCs.