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Background The participation of long non-coding RNAs (lncRNAs) in progressions of chronic pain has been evaluated. We explored mechanisms of lncRNA H19 in chronic constriction injury (CCI)-induced neuropathic pain model in vivo. Methods The expressions of lncRNA H19, microRNA-141, and GLI Family Zinc Finger 2 (GLI2) in CCI rats were determined by using RT-qPCR. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used as neuropathic pain index implying mechanical allodynia and thermal hyperalgesia. The protein concentrations of IL-1β, IL-6 and TNF-α in rats were examined by ELISA assay. RT-qPCR analyzed gene expression changes of lncRNA H19, miR-141 and GLI2. Online bioinformatics predictions supported that the bindings between miR-141 and GLI2 and dual luciferase reporter method, and RNA pull-down assays determined connections within lncRNA H19, miR-141 and GLI2 in HEK 293 cells. Results LncRNA H19 was upregulated in the tissues of rats. Also, thermal hyperalgesia and mechanical allodynia were inhibited by lncRNA H19 suppression in rats. Moreover, IL-1β, IL-6 and TNF-α protein concentrations were suppressed by the downregulation of lncRNA H19 in rats. Furthermore, miR-141 was reduced in CCI rats and restored by the lncRNA H19 knockdown, suggesting the potential negative associations of miR-141 with lncRNA H19. GLI2 targeted miR-141 and GLI2 was increased in CCI rats. Additionally, the neuropathic pain was inhibited by the inhibition of GLI2 in rats, which was reversed by the miR-141 inhibitors. Conclusion LncRNA H19 aggravated the neuropathic pain of CCI rats through miR-141/GLI2 axis, implying that lncRNA H19 might be a biomarker for the inflammation-related neuropathic pain. [ABSTRACT FROM AUTHOR]

Studies have shown that microRNAs affect the development of tumors. In many cases, they can be applied as biomarkers for the diagnosis of cancer; therefore, simple and sensitive analytical methods for detection of miRNAs are necessary. In this study, miR-141, which is used to diagnose several types of cancer, was detected in water and serum samples using a biosensor designed based on streptavidin-coated magnetic beads (SMBs), complementary sequences of miR-141 and PicoGreen as the fluorescent dye. The method is relatively fast and simple. Briefly, in the presence of miR-141, the complementary sequence forms a DNA:RNA double–strand on the surface of SMBs with intercalated PicoGreen. Upon attachment of the PicoGreen, the fluorescence intensity increased significantly (1000-fold). In the absence of a target, only single-stranded DNA (complementary strand of miR-141) existed on the surface of the SMBs. The fluorescence of the PicoGreen was low. The results revealed that the detection limits of the biosensor for miR-141 were 70 and 113.8 nmol L−1 in deionized water and serum samples, respectively. The schematic shows that in the presence of miR-141, a double-stranded structure formed on the surface of magnetic beads and upon attachment of PicoGreen a strong increase in fluorescence intensity is observed. In the absence of miR-141, a weak fluorescence was recorded. Image 1 • miRNAs have an important role in the occurrence, progression and metastasis of cancers. • A fluorescent sensor was developed for detection of miR-141 using streptavidin magnetic beads and PicoGreen. • The Biosensor showed good selectivity towards miR-141. • The detection limits of the biosensor for miR-141 was 113.8 nmol L−1 for serum samples. [ABSTRACT FROM AUTHOR]

Abstract Aims The roles of miR-141 in various types of cancers and inflammatory bowel diseases are researched, whereas, little information about its function in lung inflammation is available. This study was designed to explore the effect of miR-141 on inflammation injury in WI-38 cells, possibly providing basis for targeted therapeutic strategy for treatment of infantile pneumonia. Main methods WI-38 cells were treated with LPS to construct cell model with inflammation injury. Expressions of miR-141 and NOX2 were altered by transfection assay and expressions of them were detected by qRT-PCR or Western blot. Cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometry, respectively. The tested pro-inflammatory factors were analyzed by qRT-PCR and Western blot; and their productions were quantified by ELISA. Main proteins participating in regulation of apoptosis, p38 MAPK pathway and NF-κB pathway were analyzed by Western blot. Key findings miR-141 was down-regulated in LPS-treated cells and elevating miR-141 level reduced inflammation extent of WI-38 cells by promoting viability, inhibiting apoptosis, and inhibiting production of tested pro-inflammatory cytokines. NOX2 was up-regulated by miR-141 overexpression. NOX2 silence impaired the cell-protective effect of miR-141. miR-141 inhibited LPS-induced activations of p38 MAPK and NF-κB pathways, which was also mediated by NOX2. Significance miR-141 alleviated LPS-induced inflammation injury in WI-38 fibroblasts by up-regulating NOX2 and further inhibiting p38 MAPK and NF-κB pathways. Highlights • miR-141 protects WI-38 cells against LPS-induced inflammation injury. • NOX2 is involved in miR-141-mediated inflammation in WI-38 cells. • miR-141 inhibits p38 MAPK and NF-κB signaling pathways by up-regulating NOX2. [ABSTRACT FROM AUTHOR]

The existence of drug resistance is the main reason for chemotherapeutic failure in malignancies. Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is implicated with tumorigenesis and chemoresistance. In the present study, we aimed to identify the role of MEG3 in oxaliplatin-resistant colorectal cancer (CRC) and its potential mechanisms. MEG3 was down-regulated in oxaliplatin-resistant CRC tissues and cell lines. Low MEG3 expression was correlated with poor prognosis of CRC patients. Overexpression of MEG3 improved oxaliplatin sensitivity of HT29/OXA and HCT116/OXA cells. MEG3 suppressed miR-141 expression in HCT116/OXA cells. Moreover, MEG3 elevated PDCD4 expression through targeting miR-141, acting as a competing endogenous RNA (ceRNA). miR-141 inhibition or PDCD4 up-regulation could mimic the functional role in oxaliplatin resistance, which was counteracted by overexpression of MEG3. Collectively, MEG3 facilitated the sensitivity of CRC cells to oxaliplatin by regulating miR-141/PDCD4 axis, providing a novel therapeutic strategy for CRC. [ABSTRACT FROM AUTHOR]

Growing evidence shows that lncRNA XIST functions as an oncogene accelerating tumor progression. Transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) plays a key role in tumor metastasis. However, it is still unclear whether lncRNA XIST is implicated in TGF-β-induced EMT and influences cell invasion and metastasis in non-small-cell lung cancer (NSCLC). Here, we observed increased expression of lncRNA XIST and ZEB2 mRNA in metastatic NSCLC tissues. Knockdown of lncRNA XIST inhibited ZEB2 expression, and repressed TGF-β-induced EMT and NSCLC cell migration and invasion. Being in consistent with the in vitro findings, the in vivo experiment of metastasis showed that knockdown of lncRNA XIST inhibited pulmonary metastasis of NSCLC cells in mice. In addition, knockdown of ZEB2 expression can inhibit TGF-β-induced EMT and NSCLC cell migration and invasion. Mechanistically, lncRNA XIST and ZEB2 were targets of miR-367 and miR-141. Furthermore, both miR-367 and miR-141 expression can be upregulated by knockdown of lncRNA XIST. Taken together, our study reveals that lncRNA XIST can promote TGF-β-induced EMT and cell invasion and metastasis by regulating miR-367/miR-141-ZEB2 axis in NSCLC. [ABSTRACT FROM AUTHOR]

• Synthesis and characterization of Go and GoQdot based system. • A simple and sensitive electrochemical sensor developed for the detection of microRNA. • GoQdot modified and thiol-ssDNA detection probes on screen printed electrode. • Easy implementation of SPE to mobile phone integration. Among all cancer forms, pancreatic cancer has one of the highest mortality rates. Early pancreatic cancer detection is crucial at this time. For this purpose, in this study, a simple and sensitive electrochemical sensor was developed for the detection of microRNA (miRNAs-(miR-141)), which is a pancreatic cancer biomarker. Graphene oxide quantum dots (GoQdot) modified and thiolated single-stranded DNA detection probes (thiol-ss-DNA) on Screen Printed Electrode (SPE) interacted with miR-141 and gave significant results on electron transfer. Differential Pulse Voltammetry (DPV) and Cyclic Voltammetry (CV) measurements showed that the binding of ss-DNA to SPE and the concentration-dependent increase of miR-141 decreased electron transfer. The current values obtained for 2.3 and 6.1 nM miR-141 concentrations were calculated, and the detection limit (LOD) was found to be 0.091 pM and the limit of quantitation (LOQ) was calculated as 0.27 pM. Significant results were obtained by connecting to mobile devices with SPE. The resulting sensor system had label-free, fast, and easy application possibilities. This sensor system, obtained with GoQdot, has achieved innovative outputs for the early detection of this type of cancer diseases. [ABSTRACT FROM AUTHOR]

Cancer is caused by the abnormal proliferation of local tissue cells under the control of many oncogenic factors. MicroRNAs (miRNAs) are a class of evolutionarily conserved, approximately 22-nucleotide noncoding small RNAs that influence transcriptional regulationby binding to the 3′-untranslated region of target messenger RNA. As a member of the miRNA family, miR-141 acts as a suppressor or an oncomiR in various cancers and regulates cancer cell proliferation, apoptosis, invasion, and metastasis through a variety of signaling pathways, such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and constitutive activation of nuclear factor-κB (NF-κB). Target gene validation and pathway analysis have provided mechanistic insight into the role of this miRNA in different tissues. This review also outlines novel findings that suggest miR-141 may be useful as a noninvasive biomarker and as a therapeutic target in several cancers. • Regulatory mechanisms of miR-141 in cancer • Regulatory roles of miR-141 in various cancers • miR-141 as a tumor drug therapy • miR-141 as a drug resistance • miR-141 as a diagnostic marker of cancers [ABSTRACT FROM AUTHOR]

The brain responds to diabetic stress by inducing the inflammatory response. Under normal circumstances this process is tightly regulated. However, uncontrolled inflammatory responses lead to compromised function and eventual neurodegeneration. The microRNA (miR)-200 family, specifically miR-141, is differentially expressed in diseased states including cognitive decline, thereby triggering changes in downstream genes. We hypothesised that Metformin (MF) regulates the miR-141/protein phosphatase 2A (PP2A) axis, and associated NF-ĸB-mediated inflammasome expression in diabetic mice brain. Diabetes was induced by intraperitoneal injection of Streptozotocin (STZ), thereafter mice were treated with MF (20 mg/kg BW). Whole brain tissue was harvested for further analysis. In silico analysis showed that Sirt1 and PP2A are prediction targets of miR-141. Selected protein and gene expressions were established through western blotting and qPCR, respectively. Diabetic mice brain tissue demonstrated overexpression of miR-141 and related pro-inflammatory factors as well as decreased PP2A gene expression. MF was able to counteract this by regulating expression of miR-141 , PP2A , and p-tau at Ser396 protein expressions. Further experimentation revealed MF's inhibitory action on the inflammasome system by regulating the expression of the upstream controller NLRP3 , related cytokines and NF-κB signalling pathway. Collectively, we demonstrate that MF promotes neuroprotection in diabetic mice by dampening inflammatory responses through its inhibitory effects on various signalling pathways. Inflammation and Immunopharmacology, Metabolic Disorders and Endocrinology, Neuropharmacology. [Display omitted] • MF reduces expression of MiR-141 and modulates expression of PP2A. • MF provides neuroprotection by stabilising tau phosphorylation at Ser396. • MF prevents neuroinflammation through NF-ĸB mediated NLRP3 transcriptional regulation. [ABSTRACT FROM AUTHOR]

• circCRKL over expression promoted apoptosis, and repressed cell cycle, migration and invasion in prostate cancer cells. • circCRKL directly bound with miR-141. • KLF5 served as the target of miR-141. Prostate cancer (PCa) is a prevalent human malignancy in males. Circular RNA circCRKL (Hsa_circ_0001206) was reported to be lowly expressed in PCa tissues. However, the regulatory role of circCRKL in PCa is poorly defined. Levels of circCRKL, microRNA-141 (miR-141), and Kruppel-like factor (KLF5) were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell cycle progression, apoptosis, migration, and invasion were examined by Flow cytometry, Wound healing, and transwell assays. The underlying relationship between miR-141 and circCRKL or KLF5 was predicted by starBase, and then verified by a dual-luciferase reporter, RNA Immunoprecipitation (RIP), and RNA pull-down assays. The protein level of KLF5 was assessed by western blot assay. The biological role of circCRKL was detected by a xenograft tumor model in vivo. CircCRKL and KLF5 were decreased, and miR-141 was increased in PCa tissues and cells. The functional analysis discovered that the overexpression of circCRKL repressed cell cycle progression, migration, invasion, and boosted apoptosis of PCa cells. Mechanically, circCRKL could positively regulate KLF5 expression by sponging miR-141. In addition, circCRKL upregulation could hinder PCa tumor growth in vivo. These findings revealed that circCRKL inhibited the progression of PCa through upregulating KLF5 expression by sponging miR-141, elucidating a novel regulatory pathway in PCa cells. Our research suggested an underlying circRNA-targeted therapy for PCa. [ABSTRACT FROM AUTHOR]

• miR-141 overexpression improved osteoporosis of jawbones in ovariectomized rats. • miR-141 overexpression decreased RANKL, BGP and TRAP levels in serum. • miR-141 overexpression increased Runx2 and OSX expression in jawbones. • miR-141 regulated Wnt/β-catenin pathway in jawbones of ovariectomized rats. This work was aimed to investigate the effect of microRNA-141 (miR-141) overexpression in the jawbones of ovariectomized-induced osteoporosis rats and investigate the role of miR-141 in the Wnt/β-catenin pathway. Twenty-four female rats were randomly divided into the sham group, ovariectomized osteoporosis group (OP), miR-141 agonist group (miR-141), and miR-141 scramble group (Scramble). Bone mineral density (BMD) and pathological changes of the jaw were detected. Serum receptor activator of nuclear factor-B ligand (RANKL), osteoprotegerin, tartrate-resistant acid phosphatase (TRAP), and bone gla protein (BGP) levels were tested by ELISA. The expression of Runt-related transcription factor 2 (Runx2), and Osterix measured by immunohistochemistry and the expression of Wnt, β-catenin, and Dickkopf1 (DKK1) proteins was measured by Western blot. Furhter, the Wnt agonist DKK2-C2, Wnt inhibitor Endostar were used to verify the effect of miR-141 overexpression on the Wnt/β-catenin pathway. Compared with the OP group, the content of osteoprotegerin increased while the levels of RANKL, BGP, TRAP decreased in the miR-141 and DKK2-C2 groups (p < 0.05). The levels of Runx2 and Osterix increased significantly in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). Interestingly, the protein expression of Wnt and β-catenin increased while DKK1 was remarkably down-regulated in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). In contrast to the miR-141 group, the above results were reversed after treatment with the Endostar (p < 0.05). Overexpression of miR-141 could inhibit the osteoporosis of jawbones in ovariectomized rats by activating the Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

An impaired trophoblast invasion ability contributes to the development of pre-eclampsia (PE), and can be induced by the altered expression of various microRNAs (miRs). MiR-141 and CXCL12β (C-X-C motif chemokine ligand 12) signaling regulate trophoblast invasion and vascularization capabilities during PE pathogenesis; however, their interactions and underlying mechanisms of action remain unclear. We investigated how miR-141 modulates trophoblast invasion, with a focus on its interaction with CXCL12β signaling. A PE model was established by using HTR-8/SVneo cells, which were first cultured with 2% O 2 for 48 h, and then with 5% O 2. The expression of miR-141 in human villous trophoblast HTR-8/SVneo cells was modulated with mimics or an inhibitor, and analyzed by quantitative RT-PCR. CXCL12β levels were determined by ELISA. Cell apoptosis was determined by flow cytometry, and the invasion and vascularization capabilities of trophoblasts were evaluated by Transwell and tube formation assays, respectively. Binding of miR-141 with CXCL12β mRNA was verified by the dual luciferase assay. Protein levels were estimated by western blotting. MiR-141 expression was significantly induced by hypoxia in HTR-8/SVneo cells. MiR-141 was found to promote apoptosis and inhibit the invasion and vascularization abilities of HTR-8/SVneo cells under conditions of hypoxia. MiR-141 could directly bind with the 3′UTR region of CXCL12β mRNA and inhibit its translation. In addition, we proved that miR-141 could inhibit the invasion and vascularization abilities, and promote the apoptosis of HTR-8/SVneo cells by targeting CXCL12β under hypoxic conditions. Furthermore, we demonstrated that arachidonic acid could reverse the invasion and apoptosis abilities of HTR-8/SVneo cells mediated by CXCL12β during hypoxia. In terms of mechanism, MiR-141 could downregulate MMP2, p62, and LC3B expression, and upregulate ROCK1 and RhoA expression in HTR-8/SVneo cells by targeting the CXCL12β gene during hypoxia. The effects of CXCL12βon HTR-8/SVneo cells could be reversed by arachidonic acid (ARA). Induction of miR-141 by hypoxia promotes apoptosis, and inhibits the invasion and vascularization capabilities of HTR-8/SVneo cells by suppressing the CXCL12β and CXCR2/4 signaling pathways. [ABSTRACT FROM AUTHOR]