Long noncoding RNA SNHG5 promotes podocyte injury via the microRNA-26a-5p/TRPC6 pathway in diabetic nephropathy.

Podocyte injury is a characteristic pathological hallmark of diabetic nephropathy (DN). However, the exact mechanism of podocyte injury in DN is incompletely understood. This study was conducted using db/db mice and immortalized mouse podocytes. High-throughput sequencing was used to identify the differentially expressed long noncoding RNAs in kidney of db/db mice. The lentiviral shRNA directed against long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) or microRNA-26a-5p (miR-26a-5p) agomir was used to treat db/db mice to regulate the SNHG5/miR-26a-5p pathway. Here, we found that the expression of transient receptor potential canonical type 6 (TRPC6) was significantly increased in injured podocytes under the condition of DN, which was associated with markedly decreased miR-26a-5p. We determined that miR-26a-5p overexpression ameliorated podocyte injury in DN via binding to 3'-UTR of Trpc6, as evidenced by the markedly reduced activity of luciferase reporters by miR-26a-5p mimic. Then, the upregulated SNHG5 in podocytes and kidney in DN was identified, and it was proved to sponge to miR-26a-5p directly using luciferase activity, RNA immunoprecipitation, and RNA pull-down assay. Knockdown of SNHG5 attenuated podocyte injury in vitro, accompanied by an increased expression of miR-26a-5p and decreased expression of TRPC6, demonstrating that SNHG5 promoted podocyte injury by controlling the miR-26a-5p/TRPC6 pathway. Moreover, knockdown of SNHG5 protects against podocyte injury and progression of DN in vivo. In conclusion, SNHG5 promotes podocyte injury via the miR-26a-5p/TRPC6 pathway in DN. Our findings provide novel insights into the pathophysiology of podocyte injury and a potential new therapeutic strategy for DN.

LncRNA SNHG5 promotes the progression of osteosarcoma by sponging the miR-212-3p/SGK3 axis.

BACKGROUND: Long non-coding RNA (lncRNA) SNHG5 has been found to play an important role in tumors. Nevertheless, the function and mechanism of lncRNA SNHG5 in osteosarcoma (OS) remains unclear. The purpose of this study was to investigate whether lncRNA SNHG5 can regulate the occurrence and development of OS cells. METHODS: We performed quantitative real time PCR to detect the expression of lncRNA SNHG5 in OS cells. 143B, MG63 (knockdown) and U2OS, U2R (overexpression) cell lines were chosen for the function study of SNHG5. The effect of SNHG5, miR-212-3p, and SGK3 in OS cells was explored by MTT assays, clony formation, flow cytometry, transwell assays, wound healing assays, and cell spreading assays. Quantitative real-time PCR, Western blot analysis and luciferase assays were used to detect the interaction between lncRNA SNHG5 and miR-212-3p. RESULTS: In this study, knockdown of lncRNA SNHG5 suppressed the growth and metastasis of OS cells, whereas the overexpression of SNHG5 produced an opposite result. Mechanistically, lncRNA SNHG5 functions as a sponger against miR-212-3p and suppresses the miR-212-3p/SGK3 signaling pathway. Introduction of miR-212-3p mimics or inhibitors reverses SNHG5 overexpression or silences the exerted tumor promoting or suppressing effect. In addition, our results showed that the function of SNHG5 can be rescued by miR-212-3p and can regulate the growth and metastasis of OS cells via SGK3, the downstream target of miR-212-3p. CONCLUSIONS: In summary, our study demonstrated that lncRNA SNHG5 can regulate the proliferation and metastasis of OS cells through the miR-212-3p/SGK3 axis. This axis may provide a new target for future clinical treatment.

LncRNA SNHG5/miR-26a/SOX2 signal axis enhances proliferation of chondrocyte in osteoarthritis.

Chondrocyte is involved in the destruction of joints in osteoarthritis (OA) patients. The aim of this study was to explore the expression level of small nucleolar RNA host gene 5 (SNHG5) and evaluate its function in chondrocyte. In our current study, the expression levels of SNHG5, miR-26a, and SOX2 in 17 pairs of articular cartilage tissues and in the non-OA group were assessed by real-time quantitative reverse-transcription polymerase chain reaction. Results showed that the levels of SNHG5 and SOX2 were significantly downregulated in OA tissues, while the level of miR-26a was upregulated. MTT, colony formation and cell transwell assays were performed to assess the function of SNHG5 on the cell viability, growth ability, and migration capacity in CHON-001 cells. It was found that SNHG5 could promote chondrocyte cell proliferation and migration. The relationship between SNHG5 and miR-26a was confirmed by RIP and the luciferase reporter assays. SOX2 was identified as a target gene of miR-26a by the luciferase reporter assay. Rescue assay was applied to verify the relationship among SNHG5, miR-26a, and SOX2. Our current study demonstrated that SNHG5 is involved in the mechanism of OA through functioning as a ceRNA to competitively sponge miR-26a, therefore, regulating the expression of SOX2.

The Prognostic Value and Clinical Significance of lncRNA SNHG5 Expression in Patients with Multiple Malignancies: A Bioinformatic and Meta-analysis.

BACKGROUND: Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) has been identified as both a promising target for treatment and a predictor of prognosis in diverse types of cancer. The objective of this study was to assess whether lncRNA SNHG5 expression can be utilized as a prognostic biomarker for human cancer. METHODS: To ensure a thorough search of the literature for relevant English studies published before July 2023, several databases were searched, including PubMed, Web of Science, ProQuest, Cochrane Library, and Google Scholar. The study evaluated the impact of lncRNA SNHG5 on the overall survival (OS) of cancer by calculating the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). To further confirm the accuracy of the findings, the study investigated the expression profile and prognostic significance of lncRNA SNHG5 through the use of GenomicScape, OncoLnc, Kaplan-Meier plotter, and GEPIA databases. RESULTS: In this study, 995 patients were examined across a total of fourteen original studies. The findings indicated that there was a significant relationship between heightened lncRNA SNHG5 expression and reduced OS, as evidenced by both univariate and multivariate analyses (HR = 1.89; 95% CI, 1.44-2.49; p < 0.001; HR = 3.97; 95% CI, 1.80-8.73; p < 0.001, respectively). Pooled OR analysis showed a significant association between over-expression of lncRNA SNHG5 with advanced histological grade (OR = 0.28; 95% CI, 0.11-0.71; p = 0.007), present lymph node metastasis (LNM; OR = 4.28; 95% CI, 2.47-7.43; p < 0.001), and smoking history (OR = 0.27; 95% CI, 0.15-0.49; p < 0.001). Bioinformatic databases confirmed that elevated SNHG5 expression was significantly linked to poor prognosis in cancer patients, including colorectal cancer (CRC), acute myeloid leukemia (AML), and esophageal adenocarcinoma (ESAD), and a longer OS in patients with uterine corpus endometrial carcinoma (UCEC). CONCLUSION: These results suggest that lncRNA SNHG5 may serve as an adverse prognostic biomarker in several human cancers. Further investigations are needed to better understand the underlying mechanisms that link lncRNA SNHG5 to multiple malignancies.

The value of LncRNA SNHG5 as a marker for the diagnosis and prognosis of gastric cancer.

OBJECTIVE: To elucidate the value of serum lncRNA SNHG5 as a marker for the diagnosis and prognosis in gastric cancer. METHODS: From January 2017 to January 2018, serum samples were collected from 50 cases of gastric cancer patients and 50 cases of benign gastrosia who underwent operations in our hospital, and 50 cases of healthy person. We detected the expression level of serum lncRNA SNHG5 in all research targets and the expression levels of LncRNA SNHG5 in the cancer adjacent tissues and cancer tissues of gastric cancer patients to analyze the relationship between serum LncRNA SNHG5 level and clinicopathological parameters. ROC curve was used to analyze its prognostic value of patients with gastric cancer, while Cox regression model was used to analyze the survival predictors of short-term adverse events. RESULTS: The expression of lncRNA SNHG5 in the serum of gastric cancer was down-regulated, lower than that in the benign gastrosia group and healthy group (P < 0.05). The relative expression of lncRNA SNHG5 in cancer tissues was down-regulated compared with that in adjacent tissues (P < 0.05). lncRNA SNHG5 was correlated with drinking history and TNM stage (P < 0.05). The difference of serum lncRNA SNHG5 15 days and 1 month after operation was significant (P3 = 0.0001, P4 = 0.0135). The relative expression of serum lncRNA SNHG5 in the death group was noticeably lower than that in the survival group (P < 0.05). lncRNA SNHG5 is a survival predictor of short-term adverse events in patients with gastric cancer. CONCLUSION: The expression of lncRNA SNHG5 in gastric cancer patients before operation and those with poor prognosis decreased. Therefore, it is of high diagnostic value in prognosis prediction and is expected to become a new molecular marker for early diagnosis of gastric cancer.

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

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.

Long non-coding RNA SNHG5 affects the invasion and apoptosis of renal cell carcinoma by regulating the miR-363-3p-Twist1 interaction.

Non-coding RNA dysregulation is associated with many human diseases, including cancer. This study explored the effects of lncRNA SNHG5 on clear cell renal cell carcinoma (ccRCC). We found that lncRNA SNHG5 is upregulated in human ccRCC tissues and that lncRNA SNHG5 inhibition reduced ccRCC cell invasion and promoted apoptosis in vitro. Bioinformatics database searching revealed that lncRNA SNHG5 is predicted to regulate the interaction between miR-363-3p and Twist1. We further verified a ccRCC biomarker panel, which consists of lncRNA SNHG5, miR-363-3p, and Twist1 in ccRCC tissue samples. The direct SNHG5-miR-363-3p and Twist1-miR-363-3p interactions were confirmed via dual-luciferase reporter assays. Additionally, functional assays demonstrated that SNHG5 promotes cell invasion and inhibits apoptosis, while miR-363-3p inhibits cell invasion and promotes apoptosis via an interaction with Twist1. Furthermore, we found that Twist1 promotes tumor metastasis by regulating matrix metalloproteinase (MMP)2 and MMP9 levels. Together, these results suggest that lncRNA SNHG5 may predict ccRCC patient clinical outcome and serve as a novel anti-ccRCC therapeutic target.

LncRNA SNHG5 affects cell proliferation, metastasis and migration of colorectal cancer through regulating miR-132-3p/CREB5.

We aimed at the effects of long non-coding RNA (lncRNA) SNHG5 on proliferation, metastasis and migration of colorectal cancer (CRC) cells. We also investigated regulatory relationships among miR-132-3p, SNHG5 and CREB5 and their roles in CRC. 25 pairs of samples containing CRC tissues and matched para-tumor tissues were obtained to examine SNHG5, miR-132-3p and CREB5 expression by qRT-PCR or Western blot. The targeted relationship between miR-132-3p and SNHG5 or CREB5 was confirmed by dual luciferase report assay as well as RNA pull down assay. The expression of SNHG5, miR-132-3p and CREB5 in CRC cells were regulated by cell transfection. CRC cellular proliferation was assayed by CCK-8 and meanwhile flow cytometry was adopted to observe apoptosis. Metastasis and migration of CRC cells were determined respectively by means of Transwell assay and scratch test. The effects of SNHG5 on CRC were researched in vivo, too. SNHG5 or CREB5 was up-regulated in CRC tissues and cells, whereas miR-132-3p was down-regulated. Overexpression of SNHG5 and CREB5 resulted in the enhancement of proliferation, metastasis, migration and the inhibition of apoptosis in CRC cells, while miR-132-3p led to the opposite result. LncRNA SNHG5 promoted proliferation, migration and metastasis of CRC cells but inhibited apoptosis by modulating miR-132-3p/CERB5.

LncRNA SNHG5 enhances astrocytes and microglia viability via upregulating KLF4 in spinal cord injury.

This study aims to explore the role and mechanism of lncRNA SNHG5 in spinal cord injury (SCI). The interaction between SNHG5 and Krüppel-like factor 4 (KLF4) was verified by RNA pull-down and RNA immunoprecipitation (RIP) assay. Rat neural function was evaluated by BBB and BMS scores. Results showed that GFAP and Iba-1 (specific proteins for astrocytes and microglia respectively) were upregulated in spinal cord of SCI rats. Simultaneously, spinal cord also expressed substantially higher levels of SNHG5, KLF4 and eNOS (endothelial Nitric Oxide Synthase) than sham group. In traumatically injured astrocytes and microglia, SNHG5 overexpression increased cells viability, which was significantly inhibited by SNHG5 knockdown. KLF4 is a directly target for SNHG5 and is positively regulated by SNHG5. The knockdown of KLF4 effectively decreased astrocytes and microglia viability induced by SHNG5 overexpression and attenuated the pcDNA-SNHG5-mediated repression of the apoptosis. In SCI rats, the injection of Lenti-SNHG5 reduced BBB and BMS scores and also enhanced the protein expression of KLF4, eNOS, GFAP and Iba-1. In summary, our data suggested that SNHG5 promotes SCI via increasing the viability of astrocytes and microglia. The mechanism by which SNHG5 works is its directive interaction to KLF4 and contribution to eNOS upregulation.