LncRNA NEAT1 promotes proliferation, migration, and invasion of laryngeal squamous cell carcinoma cells through miR-411-3p/FZD3-mediated Wnt signaling pathway.

The lncRNA NEAT1 has been shown to promote the progression of several cancers, containing laryngeal squamous cell carcinoma (LSCC). However, the precise mechanism by which it promotes LSCC progression remains unclear. In this study, we verified the high expression of lncRNA NEAT1 in LSCC tissues and cells using RT-qPCR. Analysis of clinical data exhibited that high expression of lncRNA NEAT1 was associated with a history of smoking, worse T stage, lymph node metastasis, and later TNM stage in patients with LSCC. The promotion effect of lncRNA NEAT1 on LSCC cell proliferation, migration, invasion, and tumor growth in vivo was verified by CCK-8, plate clone formation, Transwell, and nude mouse tumorigenicity assays. Bioinformatics prediction and double luciferase reporter gene assay verified the binding of miR-411-3p to lncRNA NEAT1 and FZD3 mRNA, and inhibition of miR-411-3p reversed the inhibitory effect of lncRNA NEAT1 on FZD3 expression in LSCC cells. We also verified that lncRNA NEAT1-mediated FZD3 activation in the Wnt pathway affects LSCC development. In conclusion, we demonstrate that lncRNA NEAT1 promotes the progression of LSCC, and propose that the lncRNA NEAT1/miR-411-3p/FZD3 axis may be an effective target for LSCC therapy.

Circ_0056618 enhances PRRG4 expression by competitively binding to miR-411-5p to promote the malignant progression of colorectal cancer.

The purpose of this paper was to explore the role of circ_0056618 and associated mechanisms in colorectal cancer (CRC). The expression of circ_0056618, proline rich and Gla domain 4 (PRRG4) mRNA and miR-411-5p was measured by quantitative real-time PCR (qPCR).The protein levels of PRRG4 and epithelial-mesenchymal transition (EMT)-related markers were detected by western blot. Cell proliferation was assessed by cell counting kit-8, EdU, and colony formation assays. Cell migration and invasion were assessed by transwell assay. Cell apoptosis was detected by flow cytometry assay. The putative relationship between miR-411-5p and circ_0056618 or PRRG4 was verified by dual-luciferase reporter assay. The effects of circ_0056618 on tumor growth in vivo were determined by animal study. Circ_0056618 and PRRG4 was upregulated, while miR-411-5p was downregulated in CRC tumor tissues and cells. Circ_0056618 knockdown or PRRG4 knockdown inhibited CRC cell proliferation, migration/invasion, EMT, and survival. Circ_0056618 positively modulated PRRG4 expression by targeting miR-411-5p. MiR-411-5p absence or PRRG4 overexpression could rescue circ_0056618 knockdown-induced inhibition on proliferation, migration/invasion, and EMT in CRC cells. Animal assay showed circ_0056618 knockdown impeded tumor growth in vivo. Circ_0056618 promoted CRC growth and development by upregulating PRRG4 expression via competitively targeting miR-411-5p.

LINC00664/miR-411-5p/KLF9 feedback loop contributes to the human oral squamous cell carcinoma progression.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is one of the most aggressive head and neck cancers with high incidence. Multiple studies have revealed that long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis. However, the role of long intergenic non-protein coding RNA 664 (LINC00664) on the progression of OSCC was still unclear. SUBJECTS AND METHODS: In this study, the expression of LINC00664 in OSCC tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The functional role of LINC0664 was estimated by cell counting kit-8 (CCK-8), transwell assays, Western blot in vitro, and xenograft tumor model in vivo. The regulatory mechanism was investigated by RNA-binding protein immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and luciferase reporter assays. RESULTS: LINC00664 was found to be upregulated in OSCC tissues and cell lines and was associated with poor prognosis of OSCC patients. LINC00664 knockdown suppressed OSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, Kruppel like factor 9 (KLF9) enhanced LINC00664 expression at transcription level. Interestingly, LINC00664 upregulated KLF9 expression by sponging miR-411-5p. In addition, knockdown of LINC00664 restrained tumor growth of OSCC in vivo. CONCLUSION: Our study identified the oncogenic roles of LINC00664 in OSCC tumorigenesis and EMT via KLF9/LINC00664/miR-411-5p/KLF9 feedback loop, which provides new perspectives of the potential therapeutic target for OSCC.

lncRNA MIAT targets miR-411-5p/STAT3/PD-L1 axis mediating hepatocellular carcinoma immune response.

Emerging evidences have shown that long noncoding RNA (lncRNA) plays an important role in the immune escape of cancer cells. Our previous study has demonstrated that lncRNA MIAT is associated with the immune infiltration of hepatocellular carcinoma (HCC). However, the underlying mechanism of MIAT regulating the PD-L1-mediated immune escape of HCC is poorly understood. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of MIAT and PD-L1 mRNA in HCC. The relationship between MIAT, miR-411-5p, STAT3 and PD-L1 was explored by dual-luciferase reporter assay, cytotoxicity assay, Western blot and RNA immunoprecipitation (RIP). In addition, the xenograft model was established to determine the effect of MIAT on PD-L1 expression in vivo. We found that MIAT and PD-L1 were significantly upregulated in HCC tissues and the expression of PD-L1 was regulated by MIAT. The knockdown of MIAT enhanced the cytotoxicity of T cells on HCC cells. MIAT negatively regulated miR-411-5p expression, upregulated STAT3 and ultimately increased PD-L1 expression from the transcription level. The inhibition of miR-411-5p reversed STAT3 and PD-L1 expression inhibited by MIAT knockdown in HCC cells. This study suggests a novel lncRNA-mediated mechanism for HCC cells to evade the immune response; MIAT/miR-411-5p/STAT3/PD-L1 may be a novel therapeutic target for HCC.

PM2.5 promotes Drp1-mediated mitophagy to induce hepatic stellate cell activation and hepatic fibrosis via regulating miR-411.

BACKGROUND: Particulate matter≤ 2.5 µm (PM2.5) is a type of environmental agent associated with air pollution, which induces hepatic fibrosis. However, the function and mechanism of PM2.5 on hepatic stellate cell (HSC) proliferation and fibrosis remain largely unknown. METHODS: Human HSC line (LX-2) and murine HSCs were exposed to various doses of PM2.5. microRNA (miR)-411 expression was detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation, fibrosis, mitochondrial dynamics dysfunction and mitophagy were determined via cell counting kit-8 (CCK-8), qRT-PCR, Western blotting and immunofluorescence. RESULTS: PM2.5 facilitated HSC proliferation and fibrosis via increasing the levels of ACTA2, Collagen 1, TIMP1 and TGF-ß1. PM2.5 reduced miR-411 expression, and contributed to mitochondrial dynamics dysfunction via increasing Drp1 and decreasing OPA1, TOM20 and PGC-1α levels. PM2.5 promoted mitophagy by upregulating the levels of Beclin-1, LC3II/I, PINK1 and Parkin. miR-411 overexpression or autophagy blockage using 3-methyladenine (3-MA) relieved PM2.5-mediated cell proliferation and fibrosis-associated factor expression in HSCs. Drp1 was targeted by miR-411. miR-411 mitigated PM2.5-induced mitophagy via targeting Drp1. Drp1 overexpression abolished the inhibitory role of miR-411 in cell proliferation and fibrosis-associated factor levels in HSCs. CONCLUSION: PM2.5 induced HSC activation and fibrosis via promoting Drp1-mediated mitophagy by decreasing miR-411, thereby causing liver fibrosis.

LncRNA SLC16A1-AS1 contributes to the progression of hepatocellular carcinoma cells by modulating miR-411/MITD1 axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy with high morbidity. The current study aimed to explore the molecular mechanism of lncRNA SLC16A1-AS1 in the tumorigenesis of HCC. MATERIAL AND METHODS: The expression of SLC16A1-AS1 and miR-411 was examined in clinical HCC tissues. HCC cell lines Hep3B and Huh-7 were employed and transfected with si-SLC16A1-AS1. The correlation between SLC16A1-AS1 and miR-411 was verified by luciferase reporter assay. Cell viability was detected by CCK-8 assay. Cell migration and invasion capacity were examined by transwell assay. The protein level of MITD1 was analyzed by western blotting. RESULTS: The expression of SLC16A1-AS1 markedly increased in HCC tissues and cell lines. Subsequent studies identified SLC16A1-AS1 as a downstream target of miR-411. In addition, SLC16A1-AS1 knockdown and miR-411 overexpression significantly stagnated the progression of HCC cells. SLC16A1-AS1 knockdown also downregulated MITD1 levels. CONCLUSION: Our findings showed that SLC16A1-AS1 was overexpressed in HCC cells and tissues. SLC16A1-AS1 promoted the malignant characteristics of HCC cells and acted as an oncogene. Its regulatory effect may be associated with miR-411/MITD1 axis. Therefore, SLC16A1-AS1 has the potential to be used as a biomarker or therapeutic target for the treatment of HCC.

Circ_0076305 facilitates prostate cancer development via sponging miR-411-5p and regulating PGK1.

Abnormal expression of circular RNA (circRNA) is tightly linked to cancer progression. In this study, we aimed to investigate the biological role of circ_0076305 in prostate cancer (PCa). RT-qPCR was utilized to examine circ_0076305, microRNA-411-5p (miR-411-5p) and phosphoglycerate kinase 1 (PGK1) expression in PCa tissues and cells. CCK-8 assay, EdU assay, wound-healing assay and flow cytometry were executed to investigate the regulatory function of circ_0076305 on the proliferation, migration and apoptosis of PCa cells. Western blot (WB) assay was applied for measuring the protein levels. The effect of circ_0076305 on cellular glycolysis was examined using commercial kits. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were conducted for confirming the association between miR-411-5p and circ_0076305 or PGK1. The role of circ_0076305 in vivo was detected via establishing mice xenograft model. Circ_0076305 was highly expressed in PCa. Circ_0076305 silencing could repress cell growth, migration and glycolysis while triggered apoptosis in PCa cells. MiR-411-5p was targeted by circ_0076305, and miR-411-5p suppression counteracted the influence of circ_0076305 silencing in PCa cells. Additionally, miR-411-5p directly targeted PGK1, and miR-411-5p upregulation restrained PCa cell malignant behaviours via reducing PGK1. Mechanically, circ_0076305 sponged miR-411-5p to affect PGK1 expression. Importantly, circ_0076305 interference inhibited tumour growth in vivo. Circ_0076305 served as a novel oncogene PCa progression through regulation of miR-411-5p/PGK1 axis.

MicroRNA-411-3p inhibits bleomycin-induced skin fibrosis by regulating transforming growth factor-ß/Smad ubiquitin regulatory factor-2 signalling.

Skin fibrosis, which is characterized by fibroblast proliferation and increased extracellular matrix, has no effective treatment. An increasing number of studies have shown that microRNAs (miRNAs/miRs) participate in the mechanism of skin fibrosis, such as in limited cutaneous systemic sclerosis and pathological scarring. The objective of the present study was to determine the role of miR-411-3p in bleomycin (BLM)-induced skin fibrosis and skin fibroblast transformation. Using Western blot analysis and real-time quantitative polymerase chain reaction assess the expression levels of miR-411-3p, collagen (COLI) and transforming growth factor (TGF)-ß/Smad ubiquitin regulatory factor (Smurf)-2/Smad signalling factors both in vitro and in vivo with or without BLM. To explore the regulatory relationship between miR-411-3p and Smurf2, we used the luciferase reporter assay. Furthermore, miR-411-3p overexpression was identified in vitro and in vivo via transfection with Lipofectamine 2000 reagent and injection. Finally, we tested the dermal layer of the skin using haematoxylin and eosin and Van Gieson's staining. We found that miR-411-3p expression was decreased in bleomycin (BLM)-induced skin fibrosis and fibroblasts. However, BLM accelerated transforming growth factor (TGF)-ß signalling and collagen production. Overexpression of miR-411-3p inhibited the expression of collagen, F-actin and the TGF-ß/Smad signalling pathway factors in BLM-induced skin fibrosis and fibroblasts. In addition, miR-411-3p inhibited the target Smad ubiquitin regulatory factor (Smurf)-2. Furthermore, Smurf2 was silenced, which attenuated the expression of collagen via suppression of the TGF-ß/Smad signalling pathway. We demonstrated that miR-411-3p exerts antifibrotic effects by inhibiting the TGF-ß/Smad signalling pathway via targeting of Smurf2 in skin fibrosis.

Long non-coding RNA PSMA3-AS1 promotes glioma progression through modulating the miR-411-3p/HOXA10 pathway.

BACKGROUND: Glioma is a common type of brain tumor and is classified as low and high grades according to morphology and molecules. Growing evidence has proved that long non-coding RNAs (lncRNAs) play pivotal roles in numerous tumors or diseases including glioma. Proteasome 20S subunit alpha 3 antisense RNA 1 (PSMA3-AS1), as a member of lncRNAs, has been disclosed to play a tumor-promoting role in cancer progression. However, the role of PSMA3-AS1 in glioma remains unknown. Therefore, we concentrated on researching the regulatory mechanism of PSMA3-AS1 in glioma. METHODS: PSMA3-AS1 expression was detected using RT-qPCR. Functional assays were performed to measure the effects of PSMA3-AS1 on glioma progression. After that, ENCORI ( http://starbase.sysu.edu.cn/ ) database was used to predict potential genes that could bind to PSMA3-AS1, and miR-411-3p was chosen for further studies. The interaction among PSMA3-AS1, miR-411-3p and homeobox A10 (HOXA10) were confirmed through mechanism assays. RESULTS: PSMA3-AS1 was verified to be up-regulated in glioma cells and promote glioma progression. Furthermore, PSMA3-AS1 could act as a competitive endogenous RNA (ceRNA) for miR-411-3p to regulate HOXA10 and thus affecting glioma progression. CONCLUSION: PSMA3-AS1 stimulated glioma progression via the miR-411-3p/HOXA10 pathway, which might offer a novel insight for the therapy and treatment of glioma.

Dysregulation of LncRNA ANRIL mediated by miR-411-3p inhibits the malignant proliferation and tumor stem cell like property of multiple myeloma via hypoxia-inducible factor 1α.

Long non-coding RNA (lncRNA) ANRIL has been reported to be closely related to the relapse of multiple myeloma patients. However, the functional role and underlying mechanism of lncRNA ANRIL in multiple myeloma are not known. This study aims to investigate the biological function of lncRNA ANRIL in multiple myeloma. In this study, compared with normal tissues from healthy donors, lncRNA ANRIL and HIF-1α expressions were up-regulated in tumor tissues from multiple myeloma patients. miR-411-3p expression was down-regulated in tumor tissues from multiple myeloma patients. Besides, lncRNA ANRIL can interact with miR-411-3p. HIF-1α was confirmed to be a target of miR-411-3p. Correlation analysis showed that lncRNA ANRIL expression was negatively correlated with miR-411-3p expression. HIF-1α expression was negatively correlated with miR-411-3p expression. Further transfection experiments showed that knockdown of ANRIL or overexpression of miR-411-3p significantly inhibited cell proliferation, tumor formation ability and tumor stem cell like property, promoted cell apoptosis in vitro. Finally, miR-411-3p mimic reduced tumor volume, improved survival rate, suppressed malignant proliferation and tumor stem cell like property in U266 xenograft model. Our results demonstrate that lncRNA ANRIL mediated by miR-411-3p promotes the malignant proliferation and tumor stem cell like property of multiple myeloma through regulating HIF-1α.

Circ_0082182 promotes oncogenesis and metastasis of colorectal cancer in vitro and in vivo by sponging miR-411 and miR-1205 to activate the Wnt/ß-catenin pathway.

BACKGROUND: Circular RNAs (circRNAs) are a class of endogenous single-strand RNA transcripts with crucial regulation in human cancers. The objective of this study is to investigate the role of circ_0082182 in CRC and its specific functional mechanism. METHODS: The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the levels of circ_0082182, microRNA-411 (miR-411) and microRNA-1205 (miR-1205). Cell proliferation was detected by Cell counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used for determining cell cycle and cell apoptosis. Cell apoptosis was also assessed by caspase3 and caspase9 activities. Cell migration and invasion were examined using scratch assay and transwell assay. The interaction between circ_0082182 and miRNA was validated by the dual-luciferase reporter and biotinylated RNA pull-down assays. Wnt/ß-catenin pathway and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by Western blot. Xenograft model was established for the research of circ_0082182 in vivo. RESULTS: Circ_0082182 was upregulated in CRC and could predict the poor prognosis of CRC patients. Functionally, circ_0082182 promoted CRC cell proliferation, cell cycle progression, and metastasis while inhibited apoptosis. Subsequently, circ_0082182 was shown to act as the sponges of miR-411 and miR-1205. MiR-411 and miR-1205 were identified as tumor inhibitors in CRC. Furthermore, circ_0082182 promoted the CRC progression via sponging miR-411 and miR-1205. Moreover, circ_0082182 facilitated the Wnt/ß-catenin pathway and EMT process by targeting miR-411 and miR-1205. In vivo, circ_0082182 accelerated the CRC tumorigenesis and EMT process by activating the Wnt/ß-catenin pathway by downregulating the expression of miR-411 or miR-1205. CONCLUSION: This study showed that circ_0082182 functioned as an oncogene in the developing process of CRC by sponging miR-411 or miR-1205 to activate the Wnt/ß-catenin pathway. Circ_0082182 might be a molecular target in the diagnosis and treatment of CRC.

Interference with lncRNA NEAT1 promotes the proliferation, migration, and invasion of trophoblasts by upregulating miR-411-5p and inhibiting PTEN expression.

Background: Preeclampsia (PE) is an idiopathic hypertensive disorder of pregnancy, which is related to abnormal placental villi development. Our previous study has found that lncRNA NEAT1 promotes apoptosis of trophoblasts, but the role of NEAT1 in proliferation, migration, and invasion is still unclear. This study explores the role of NEAT1 in proliferation, migration, and invasion of trophoblasts.Methods: NEAT1 and miR-411-5p levels were detected by quantitative real-time PCR. Colony formation assay detected cell proliferation and transwell assay detected cell migration and invasion. Dual-luciferase reporter assay detected the binding between NEAT1 and miR-411-5p as well as the binding between miR-411-5p and PTEN. RNA pull-down assay detected the combination between NEAT1 and miR-411-5p.Result: NEAT1 was increased and miR-411-5p was reduced in PE patients and human trophoblasts (HTR8/SVneo cells) that were induced with H2O2. Interference with NEAT1 promoted cell proliferation, migration, and invasion, and the miR-411-5p inhibitor reversed the effect of siRNA-NEAT1. The expression of PTEN was promoted in PE patients and HTR8/SVneo cells that were induced with H2O2, while the miR-411-5p mimic inhibited PTEN expression, and the plasmid-mediated PTEN overexpression reversed the effect of the miR-411-5p mimic. Besides, under H2O2 induction, the miR-411-5p mimic promoted cell proliferation, migration, and invasion, and the plasmid-mediated PTEN overexpression reversed the effect of the miR-411-5p mimic.Conclusion: Interference with lncRNA NEAT1 promoted the proliferation, migration, and invasion of trophoblasts and alleviated the development of PE, which was partly mediated by upregulating miR-411-5p and inhibiting PTEN expression.

LncRNA TTN-AS1 promotes the progression of oral squamous cell carcinoma via miR-411-3p/NFAT5 axis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common kind of squamous cell carcinoma of the head and neck, which is a threat to public health. Long noncoding RNAs (lncRNAs) are associated with the development of various diseases, including cancers. LncRNA titin antisense RNA 1 (TTN-AS1) is known as a crucial regulatory factor in several cancers. Nevertheless, the specific functions of TTN-AS1 in OSCC remains obscure. METHODS: The expression of TTN-AS1 in OSCC samples or cells was analyzed through qRT-PCR. Colony formation assay, EdU assay, flow cytometry assay, TUNEL assay and wound healing assay were conducted to estimate the functions of TTN-AS1 in OSCC cells. RIP and luciferase reporter assays were utilized to detect the interaction between TTN-AS1 and miR-411-3p as well as between miR-411-3p and NFAT5. RESULTS: TTN-AS1 expression was stronger in OSCC cells. Knockdown of TTN-AS1 effectively restrained cell proliferation and migration but had inductive role in apoptosis. Moreover, TTN-AS1 could function as the miR-411-3p sponge in OSCC and miR-411-3p exerted the inhibitory functions on OSCC cell growth. In addition, NFAT5 was proven as the target of miR-411-3p. Rescue assay indicated that overexpressing NFAT5 could reverse the inhibitory function of TTN-AS1 depletion on cell growth. CONCLUSION: lncRNA TTN-AS1 contributed to the progression of OSCC via miR-411-3p/NFAT5 axis.

Long noncoding RNA CDKN2B-AS1 interacts with miR-411-3p to regulate ovarian cancer in vitro and in vivo through HIF-1a/VEGF/P38 pathway.

Ovarian cancer (OC) is one of the most prevalent cancers with high fatality rate. In the present study, RT-PCR showed that the mRNA level of CDKN2B-AS1 was significantly upregulated while the miR-411-3p was downregulated in OC cell lines. In addition, the Sh-CDKN2B-AS1 resulted in the suppression of cell growth, invasion, migration and promotion of apoptosis, and miR-411-3p showed reversed results. Further studies demonstrated that CDKN2B-AS1 could directly interact with miR-411-3p, and that there was an inverse correlation between miR-411-3p and CDKN2B-AS1. Moreover, the in vivo experiments further demonstrated that Sh-CDKN2B-AS1 could inhibit the tumor growth. In addition, we examined the effect of CDKN2B-AS1 and miR-411-3p on HIF1a/VEGF/P38 axis. Consequently, Sh-CDKN2B-AS1 could suppress this pathway. In summary, our study demonstrated that the CDKN2B-AS1 interacted with miR-411-3p contributing to carcinogenesis in OC. Meanwhile, Sh-CDKN2B-AS1 showed anti-cancer role by promoting apoptosis and inhibiting cell growth, invasion and migration. Collectively, CDKN2B-AS1 modulated these activities possibly though miR-411-3p/HIF1a/VEGF/P38 pathway.

Silencing synaptic MicroRNA-411 reduces voluntary alcohol consumption in mice.

Chronic alcohol consumption alters the levels of microRNAs and mRNAs in the brain, but the specific microRNAs and processes that target mRNAs to affect cellular function and behavior are not known. We examined the in vivo manipulation of previously identified alcohol-responsive microRNAs as potential targets to reduce alcohol consumption. Silencing of miR-411 by infusing antagomiR-411 into the prefrontal cortex of female C57BL/6J mice reduced alcohol consumption and preference, without altering total fluid consumption, saccharin consumption, or anxiety-related behaviors. AntagomiR-411 reduced alcohol consumption when given to mice exposed to a chronic alcohol drinking paradigm but did not affect the acquisition of consumption in mice without a history of alcohol exposure, suggesting that antagomiR-411 has a neuroadaptive, alcohol-dependent effect. AntagomiR-411 decreased the levels of miR-411, as well as the association of immunoprecipitated miR-411 with Argonaute2; and, it increased levels of Faah and Ppard mRNAs. Moreover, antagomiR-411 increased the neuronal expression of glutamate receptor AMPA-2 protein, a known alcohol target and a predicted target of miR-411. These results suggest that alcohol and miR-411 function in a homeostatic manner to regulate synaptic mRNA and protein, thus reversing alcohol-related neuroadaptations and reducing chronic alcohol consumption.

miR-411 suppresses acute spinal cord injury via downregulation of Fas ligand in rats.

OBJECTIVE: To explore the role of miR-411/FasL in acute spinal cord injury (ASCI). METHODS: The ASCI rat model was established, and expression of miR-411 and Fas ligand (FasL) was examined. Basso, Beattie and Bresnahan (BBB) score was used to evaluate the rats' neurological function. PC12 oxygen-glucose deprivation (OGD) model was also established. Gene manipulation (including miR-411 mimic or inhibitor) was used to modulate gene expression. Luciferase reporter assay was conducted to confirm the targeting relationship between miR-411 and FasL. Flow cytometry was applied in the measurement of PC12 cell apoptosis. Finally, the miR-411 mimic was injected into the vertebral canal of ASCI rats to determine the effects of miR-411 in vivo. RESULTS: Compared with sham group, the expression of miR-411 and FasL was significantly decreased and increased in ASCI group, respectively (P < 0.05). Similarly, the expression of miR-411 and FasL was significantly lower and higher in OGD group than that in control group, respectively (P < 0.05). miR-411 directly controlled the FasL expression. miR-411 mimic can dramatically reduce the increased percentage of apoptosis cells caused by OGD when comparing to mimic control, which was greatly reversed by the overexpression of FasL (P < 0.05). Further, the BBB score was significantly elevated in the miR-411 mimic group when comparing to mimic control group, with decreased FasL expression (P < 0.05). CONCLUSION: miR-411 mimic suppressed PC12 cell apoptosis via FasL, and relieved ASCI in rats.

Overexpression of circular RNA circ_001569 indicates poor prognosis in hepatocellular carcinoma and promotes cell growth and metastasis by sponging miR-411-5p and miR-432-5p.

Emerging evidence indicated that abnormally expressed circular RNAs (circRNAs) are critically involved in tumorigenesis and development of several cancers. However, the study relevant to the relationship between circRNAs and hepatocellular carcinoma (HCC) is rare. In this study, the expression of circ_001569 in HCC tissue specimens and cells were determined by qRT-PCR. The clinical relevance of circ_001569 was also analyzed. In addition, loss-of-function and gain-of-function assays were conducted to explore the biological functions of circ_001569. Furthermore, tumor formation and lung metastasis studies were induced to confirm the in vitro data. Mechanistically, bioinformatics analysis and luciferase reporter assays were conducted to illustrate the underlying mechanism of circ_001569. The results indicated that circ_001569 was overexpressed in HCC tissue samples and cells. This overexpression is correlated with larger tumor size, advanced TNM stages and unfavorable prognosis in the patients with HCC. Additionally, circ_001569 significantly facilitated HCC cell growth, migration and invasion. The animal studies further confirmed thein vitroresults. More importantly, circ_001569 could directly sponge miR-411-5p and miR-432-5p. The oncogenic functions of circ_001569 is partially dependent on its regulation on miR-411-5p and miR-432-5p. In summary, circ_001569/miR-411-5p/miR-432-5p regulatory signaling might be a rational HCC-related therapeutic target.

MiR-411 suppressed vein wall fibrosis by downregulating MMP-2 via targeting HIF-1α.

This study was aim to investigate the specific mechanisms of miR-411 in vein wall fibrosis remodeling. Vein wall fibrosis injury-induced deep venous thrombosis (DVT) rat model was well established. The expression of miR-411 at mRNA levels and Collagen I, hypoxia-inducible factor (HIF)-1α together with matrix metalloproteinase (MMP)-2 at protein levels in vein wall tissues and vascular smooth muscle cells (VSMCs) following transfection were determined using quantitative real-time PCR (qRT-PCR) and western blotting, respectively. Luciferase reporter assay was used to confirm the potential target of miR-411. MiR-411 mimic injected into rat model of DVT was to verify the role of miR-411 in vein wall fibrosis in vivo. MiR-411 was downregulated while Collagen I, HIF-1α and MMP-2 was upregulated in vein wall tissues and VSMCs obtained from rat model of DVT. MiR-411 overexpression in VSMCs separated from rats of vascular remodeling group (VR-VSMCs) upregulated miR-411, HIF-1α and inhibited cell proliferation and Collagen I expression, while miR-411 knockdown in VSMCs isolated from healthy rats (Control-VSMCs) reversed the effects. Furthermore, luciferase reporter assay demonstrated that HIF-1α was a target of miR-411. In addition, overexpression of miR-411 and HIF-1α in VR-VSMCs promoted HIF-1α, Collagen I expression and cell proliferation, however, tissue inhibitor of metalloproteinase (TIMP)-2 treatment led to adverse trends. MiR-411 mimic injected into rat model of DVT could suppress vein wall fibrosis in vivo. MiR-411 inhibited vein wall fibrosis by downregulating MMP-2 mediated by HIF-1α.

miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2.

miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy.

miR-411 contributes the cell proliferation of lung cancer by targeting FOXO1.

Lung cancer is the leading cause of cancer deaths worldwide; the study of microRNAs gives new hope for lung cancer treatment. miR-411 has been demonstrated to be an independent prognostic factor for lung adenocarcinoma, but the role and regulatory mechanism are largely unknown. In the present study, we found miR-411 was overexpressed in the lung cancer cells; overexpression of miR-411 promoted anchorage-dependent and anchorage-independent growths of lung cancer, while miR-411 knockdown reduced this effect. Further study showed forkhead box O1 (FOXO1) was a target of miR-411. Overexpression of miR-411 suppressed the expression of FOXO1; the effect of suppression was abrogated when the mutation occurred in the 3'UTR of FOXO1. Knockdown of FOXO1 in cells which miR-411 was inhibited recapitulated the phenotype of miR-411 overexpression. Taken together, our study revealed miR-411 promoted cell proliferation of lung cancer by targeting tumor suppressor gene FOXO1 and miR-411 might be a potential target for lung cancer therapy.