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.     

microRNA-510-5p promotes thyroid cancer cell proliferation,migration, and invasion through suppressing SNHG15

SNHG15 has been suggested to be correlated with clinical progression and prognosis, and function as tumor suppressive long noncoding RNA in thyroid cancer at our previous study. SNHG15 was proposed to be a potential target for miR-510-5p at LncBase Predicted database. Thus, the aim of this study was to explore the relationship between miR-510-5p and SNHG15 in thyroid cancer, and the clinical significance of miR-510-5p in patients with thyroid cancer. In our results, levels of miR-510-5p expression were increased in thyroid cancer tissues and cell lines compared with adjacent normal thyroid tissues and normal thyroid cell line, respectively. There was a statistically negative correlation between SNHG15 expression and miR-510-5p expression in thyroid cancer tissues. Moreover, miR-510-5p directly bound to SNHG15, and negatively regulated SNHG15 expression in thyroid cancer cells. Furthermore, miR-510-5p promoted thyroid cancer cell proliferation, migration, and invasion through suppressing SNHG15. Finally, high miR-510-5p expression was observed in tumor tissues with advanced clinical stage or lymph node metastasis. In conclusion, we provide evidence to support a pivotal role for miR-510-5p in regulating thyroid cancer cell proliferation, migration, and invasion.     

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.     

Long noncoding RNA SNHG15 promotes human breast cancer proliferation,migration and invasion by sponging miR-211-3p

Long non-coding RNAs (lncRNA) have been demonstrated to act as essential regulators in the development and progression of breast cancer. In our study, we found that long noncoding RNA SNHG15 was highly expressed in breast cancer tissues and cell lines. And the expression of SNHG15 was correlated with TNM stage, lymphnode metastasis and survival in breast cancer patients. SNHG15 knockdown significantly inhibited the proliferation and induced apoptosis in breast cancer cells in vitro and in vivo. Besides, SNHG15 downregulation suppressed cell migration and invasion in MCF-7 and BT-20 cells, and inhibited epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG15 acted as a competing endogenous RNA to sponge miR-211-3p, which was downregulated in breast cancers and inhibited cell proliferation and migration. Our results showed that there was a negative correlation between SNHG15 and miR-211-3p expression in breast cancer patients. Collectively, we, for the first time, revealed the functions of SNHG15 and miR-211-3p in breast cancer.     

SNHG1 represses the anti-cancer roles of baicalein in cervical cancer through regulating miR-3127-5p/FZD4/Wnt/β-catenin signaling

As a flavonoid, baicalein exhibits remarkable anti-cancer roles in several cancers. However, the factors regulating the antitumorigenic roles of baicalein in cervical cancer remain undefined. Here, we revealed that long noncoding RNA SNHG1 is implicated in the tumor-suppressive roles of baicalein. Functional assays demonstrated that ectopic expression of SNHG1 attenuates the roles of baicalein in repressing cervical cancer cell viability, inducing apoptosis, and repressing migration. SNHG1 silencing promotes the tumor-suppressive roles of baicalein in cervical cancer cell viability, apoptosis, and migration. Xenograft assays showed that SNHG1 reverses the tumor-suppressive roles of baicalein in repressing cervical cancer growth in vivo. Mechanistic investigations revealed that SNHG1 directly binds miR-3127-5p and up-regulates FZD4, a target of miR-3127-5p. Via regulating miR-3127-5p/FZD4, SNHG1 activates Wnt/β-catenin signaling. Moreover, SNHG1 reverses the repressive role of baicalein on Wnt/β-catenin signaling. The effect of SNHG1 on the antitumorigenic process of baicalein was abolished by Wnt/β-catenin signaling inhibitor ICG-001. Together, our observations demonstrated that SNHG1 represses the tumor-suppressive roles of baicalein in cervical cancer through regulating miR-3127-5p/FZD4/Wnt/β-catenin axis, and suggested that targeting SNHG1 represents a potential strategy to enhance the tumor-suppressive roles of baicalein in cervical cancer.Impact statementBaicalein exhibits anti-cancer roles in several cancers. However, the factors influencing the antitumorigenic efficiencies of baicalein in CC remain largely unclear. Here, we provide convincing evidences that lncRNA SNHG1 attenuates the tumor-suppressive roles of baicalein in CC cell viability, apoptosis, migration, and CC tumor growth. This study further demonstrates that the influences of SNHG1 in the antitumorigenic process of baicalein are achieved through modulating the miR-3127-5p/FZD4Wnt/β-catenin axis. SNHG1 attenuates the repressive role of baicalein on Wnt/β-catenin. Therefore, SNHG1 is a novel modulator of the tumor-suppressive roles of baicalein and SNHG1 represents a therapeutic intervention target to reinforce the tumor-suppressive roles of baicalein in CC.     

Upregulation of long noncoding RNA SNHG20 promotes cell growth and metastasis in esophageal squamous cell carcinoma via modulating ATM-JAK-PD-L1 pathway

Increasing evidence have proved that long noncoding RNAs (lncRNAs) play significant roles in tumorigenesis and development of various cancers. However, the effect of small nucleolar RNA host gene 20 (SNHG20) on the progression of esophageal squamous cell carcinoma (ESCC) remains to be discovered. Herein, we aim to find out the function and the possible mechanism of SNHG20 in ESCC progression. In our study, we demonstrate that SNHG20 is markedly upregulated in ESCC tissues and cell lines. Besides, the level of SNHG20 is closely associated with tumor size, lymph node metastasis, TNM stage, and tumor grade. In addition, SNHG20 level is an independent predictor for clinical outcomes of ESCC patients. Then the gain- and loss-of-function assays reveal that SNHG20 overexpression promotes cell proliferation, migration, invasion, and epithelial-mesenchymal transition as well as represses apoptosis, whereas depletion of SNHG20 exhibits opposite effects. Moreover, we uncover that SNHG20 modulates the expression of ataxia telangiectasia–mutated kinase (p-ATM), p-JAK1/2, and programmed cell death 1 ligand 1 (PD-L1) in ESCC cells and ATM upregulation restores the suppressive effect of SNHG20 inhibition on ESCC progression. Therefore, we conclude that SNHG20 serves as a carcinogen in ESCC by promoting growth and metastasis via ATM-JAK-PD-L1 pathway, supplying a possibly effective therapeutic target for ESCC.     

LncRNA SNHG15 modulates gastric cancer tumorigenesis by impairing miR-506-5p expression

The gastric cancer (GC) patients commonly have a poor prognosis due to its invasiveness and distant metastasis. Growing evidence proved that aberrant long non-coding RNAs (lncRNAs) expression contributes to tumor development and progression. LncRNA SNHG15 has been reported to be involved in many different kinds of cancer, while its role in GC remains unclear. In the present study, we found that SNHG15 was up-regulated in GC tissues and cell lines. Silencing SNHG15 suppressed proliferation migration, invasion and promoted apoptosis of AGS cells. More importantly, microRNA-506-5p (miR-506-5p) was predicted as a direct target of SNHG15 by binding its 3′-UTR and further verified using luciferase reporter assay. Meanwhile, the results of rescue experiments revealed that knockdown of miR-506-5p expression reversed the functional effects of SNHG15 silenced cell proliferation, migration, invasion and apoptosis. In conclusion, our findings revealed that SNHG15 executed oncogenic properties in GC progression through targeting miR-506-5p, which might provide a novel target for the GC treatment.     

Exosome-mediated lncRNA SNHG11 regulates angiogenesis in pancreatic carcinoma through miR-324-3p/VEGFA axis

Pancreatic carcinoma (PC) is one of the most common and deadly human malignancies worldwide. LncRNAs play significant roles in the occurrence and development of various cancers. LncRNA SNHG11 (SNHG11) has been found to display high expression in serum of PC patients, which implies that dysregulated SNHG11 may be related to the development of PC. However, there is still a knowledge gap concerning the specific function and molecular mechanism of SNHG11 in PC. After conducting experiments with constructed models in vitro or in vivo, we found that exosomal SNHG11 promoted cell proliferation, migration, and angiogenesis but impeded cell apoptosis in PC in vitro, and additionally, it facilitated tumor growth in vivo. Exosome-mediated SNHG11 regulated the expression of VEGFA through sponging miR-324-3p. Rescue assays validated that the inhibitory effect of SNHG11 depletion on cell proliferation, migration, and angiogenesis could be reversed by miR-324-3p downregulation or VEGFA upregulation, and the promoting effect of SNHG11 silence on cell apoptosis could be rescued by transfection of miR-324-3p inhibitor or pcDNA3.1-VEGFA. To conclude, exosomal-mediated SNHG11 could regulate PC progression via miR-324-3p/VEGFA axis. Our findings may provide a novel insight for understanding PC, which might contribute to the development of potential PC biomarker.     

Up-regulated lnc-SNHG1 contributes to osteosarcoma progression through sequestration of miR-577 and activation of WNT2B/Wnt/β-catenin pathway

Long noncoding RNA small nucleolar RNA host gene 1 (lnc-SNHG1) was reported to play an oncogenic role in the progression of cancers. However, the roles of SNHG1 and its molecular mechanism in osteosarcoma (OS) cells are largely unknown. In present study, we found that the expression of SNHG1 was up-regulated in OS tissues and cell lines. OS patients with the high SNHG1 expression were positively correlated with tumor size, TNM stage and lymph node metastasis. In addition, SNHG1 overexpression promoted cell proliferation, cell migration and EMT process in U2OS and MG63 cells and tumor growth in vivo. Furthermore, we also found that miR-577 could act as a ceRNAof SNHG1 in OS cells and the promotion of OS progression induced by lnc-SNHG1 overexpression required the inactivity of miR-577. Besides, we identified that WNT2B acted as a target of miR-577, and WNT2B played the oncogenic role in OS cells by activating Wnt/β-catenin pathway. In short, our study suggested that lnc-SNHG1 could promote OS progression via miR-577 and WNT2B. The lnc-SNHG1/miR-577/WNT2B/Wnt/β-catenin axis regulatory network might provide a potential new therapeutic strategy for OS treatment.     

lncRNA SNHG3 facilitates acute myeloid leukemia cell growth via the regulation of miR-758-3p/SRGN axis

Small nucleolar RNA host gene 3 (SNHG3) is a newly identified long non-coding RNA whose dysregulation has been reported in several cancers. However, the details about clinical significances and biological functions of SNHG3 on acute myeloid leukemia (AML) remain covered. In this study, we revealed increased SNHG3 expression in AML samples and cells and its high potential as a prognostic biomarker for AML patients. Likewise, serglycin (SRGN), which plays an important role in granule-mediated apoptosis, was previously verified to be upregulated in AML and confirmed again by the present study, and its upregulation predicted poor outcomes in AML. Furthermore, knockdown of SNHG3 or SRGN inhibited cell proliferation and induced cell apoptosis. Besides, silencing SNHG3 noticeably decreased the expression of SRGN in AML cells. Moreover, we uncovered that SNHG3 modulated SRGN expression by competitively binding with miR-758-3p. Importantly, both miR-758-3p suppression and SRGN overexpression could mitigate the inhibitory effects of SNHG3 depletion on AML cell growth. Intriguingly, the higher SRGN expression in AML samples with a higher SNHG3 level exhibited an enhanced Ki67 level but a reduced caspase 3 level. To sum up, SNHG3 elicits a growth-promoting function in AML via sponging miR-758-3p to regulate SRGN expression, providing a new therapeutic road for AML patients.     

Long noncoding RNA lnc-ABCA12-3 promotes cell migration,invasion, and proliferation by regulating fibronectin 1 in esophageal squamous cell carcinoma

Long noncoding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). We previously demonstrated that a novel lncRNA, lnc-ABCA12-3, was overexpressed in ESCC tissues. However, the exact function of lnc-ABCA12-3 is unknown. In the current study, we aimed to evaluate the expression of lnc-ABCA12-3 in ESCC and to explore the potential mechanism of lnc-ABCA12-3 in cell migration, invasion, and proliferation. We showed that lnc-ABCA12-3 was upregulated in ESCC tumor tissues and cell lines. The increased expression of lnc-ABCA12-3 was positively associated with advanced tumor-node-metastasis stages and poor prognosis. The knockdown of lnc-ABCA12-3 inhibited the cell migration, invasion, and proliferation abilities of KYSE-510 and Eca-109 cells. We also found that fibronectin 1 (FN1) was upregulated in ESCC tumor tissues. The expression of FN1 messenger RNA was positively correlated with the expression of lnc-ABCA12-3 in ESCC tumor tissues. After lnc-ABCA12-3 knockdown, the expression of FN1 was downregulated. In addition, the overexpression of FN1 restored the abilities of cell migration, invasion and proliferation in Eca-109 cells. Further studies indicated that lnc-ABCA12-3 acted as a competing endogenous RNA for miR-200b-3p to regulate FN1 expression. In conclusion, these results suggest that lnc-ABCA12-3 is a novel oncogene in tumorigenesis and that its high expression is related to a poor prognosis for patients with ESCC. lnc-ABCA12-3 promotes cell migration, invasion, and proliferation via the regulation of FN1 in ESCC. Our data suggest that lnc-ABCA12-3 might serve as a potential prognostic biomarker and therapeutic target for ESCC.     

LncRNA SNHG1 regulates immune escape of renal cell carcinoma by targeting miR-129-3p to activate STAT3 and PD-L1

Immune escape of renal cell carcinoma (RCC) impacts patient survival. However, the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in RCC immune escape remains unclear. Quantitative real-time PCR and western blotting results revealed that the expression of lncRNA SNHG1 and STAT3 were upregulated in RCC tissues and cells and that the expression of miR-129-3p was downregulated. Enzyme-linked immunosorbent assay results revealed the increased levels of immune-related factors (interferon-γ, tumour necrosis factor α, and interleukin-2) in RCC tissues. SNHG1 knockdown or miR-129-3p overexpression inhibited the proliferation and invasion of A498 and 786-O cells, while the proliferation and cytotoxicity of CD8⁺ T cells increased, which promoted the secretion of immune-related factors. STAT3 overexpression decreased the protective effect of miR-129-3p overexpression on RCC cell immune escape. In addition, miR-129-3p knockdown and STAT3 overexpression decreased the protective effect of lncRNA SNHG1 knockdown on RCC cell immune escape. In addition, PD-L1 expression was downregulated after lncRNA SNHG1 knockdown but upregulated after miR-129-3p knockdown and STAT3 overexpression. Dual-luciferase assays showed that lncRNA SNHG1 targets miR-129-3p, and miR-129-3p targets STAT3. RNA pull-down and RNA immunoprecipitation assays verified the regulatory relationship between SNHG1 and STAT3. In vivo, shSNHG1 prolonged the overall survival of RCC tumour model mice and inhibited RCC tumour growth and immune escape but increased CD8⁺ T cell infiltration in mice. Our findings provide an experimental basis for elucidating the molecular mechanisms of immune escape by RCC and reveal a novel target to treat this disease.