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Background: Lung cancer mainly includes non-small cell lung cancer (NSCLC). Lung adenocarcinoma (LUAD) is the main subtype of NSCLC. Long non-coding RNAs (LncRNAs) had been found to exert numerous functions on the progressions of cancers. MicroRNAs often exist as the target of LncRNAs to regulate a series of signaling pathways in human. We explored the effects and molecular mechanism of LncRNA SGMS1-AS1 on the procedures of LUAD cells. Methods: The ENCORI and GEPIA databases were used to analyze the differences in SGMS1, miR-106a-5p, and MYLIP between LUAD and normal tissue. Their expression levels were examined by RT-PCR. CCK8, colony formation, migration, and invasion assay were conducted in LUAD cells which had silenced SGMS1-AS1. To verify the relationship between SGMS1-AS1, miR-106a-5p, and MYLIP, we overexpressed miR-106a-5p inhibitor or MYLIP in LUAD cells after decreasing SGMS1-AS1 and repeated the above assays. Results: SGMS1-AS1 was downregulated in LUAD tissue as well as cells, which was related to good prognosis of patients with lung adenocarcinoma. Additionally, knockdown of SGMS1-AS1 promoted proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression of LUAD cells, which meant that SGMS1-AS1 inhibited the progression of LUAD cells. Furthermore, miR-106a-5p was the direct target of SGMS1-AS1 and transfecting miR-106a-5p inhibitor could reversed the impact induced by knockdown of SGMS1-AS1. Subsequently, we found that MYLIP was the target of miR-106a-5p, which was negatively correlated with miR-106a-5p, but had high positive correlation with SGMS1-AS1. Consistently, overexpression MYLIP partly eliminated the effects on A549 cells induced by silencing of SGMS1-AS1. Conclusion: LncRNA SGMS1-AS1 inhibits the proliferation, invasion, migration and EMT progression of LUAD cells via targeting miR-106a-5p/MYLIP axis. [ABSTRACT FROM AUTHOR]

Objective(s): Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS.Recent evidence indicates that Interleukin 17 (IL-17)-producing T helper cells (Th17 cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th17 and Treg differentiation, the role of microRNAs in MS is not completely understood. Thereby, as a step closer, we analyzed the expression profile of miR-9-5p and miR-106a-5p, and protein level of retinoic acid receptor (RAR)-related orphan receptor C (RORC; Th17 master transcription factor) as direct target of miR-106a-5p and forkhead box P3 (FOXP3; Treg master transcription factor) as indirect target of miR-9-5p in CD4+ T cells in two groups of relapsing and remitting in our relapsing-remitting MS (RR-MS) patients. Materials and Methods:Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to assess the expression of miRNAs and mRNAs, in 40 RR-MS patients and 11 healthy individuals. Thus, FOXP3 and RAR-related orphan receptor γt (RORγt) was assessed in CD4+T-cells by flow cytometry. We also investigated the role of these miRNAs in Th17/Treg differentiation pathway through bioinformatics tools. Results: An up-regulation of miR-9-5p and down-regulation of miR-106a-5p in relapsing phase of MS patients were observed compared to healthy controls. RORC and FOXP3 wereup-regulated in relapsing and remitting phases of MS, respectively. Conclusion: Expression pattern of miR-9-5p and miR-106a-5p and their targets suggest a possible inducing role of miR-9-5p and suppressing role of miR-106a-5p in differentiation pathway of Th17 cells during MS pathogenesis.

Although stable microRNAs (miRNAs) are present in human peripheral blood and have been considered as novel biomarkers for various diseases. But there is little research about miRNAs as biomarkers of mesangial proliferative glomerulonephritis (MsPGN). This study aimed to identify whether there exist disordered circulating miRNAs that can function as biomarkers for MsPGN disease activity. The candidate miRNAs were validated in 70 MsPGN patients and 70 healthy controls by quantitative real-time PCR (RT-qPCR). The specificity and sensitivity of the miRNA panel was assessed by receiver operating characteristic (ROC) curves. In addition, the candidate miRNA levels were measured in the different MsPGN progression and in the membranous nephropathy (MN) patients and the hypothetical role of the candidate miRNA on mesangial cell proliferation was analysed. Situ hybridization was performed to examine the candidate miRNA levels in the glomerulus. These results showed that miR-106a-5p and miR-30a-5p were highly expressed in MsPGN patients compared with healthy controls and could discriminate MsPGN from healthy controls with an area under the ROC curve (AUC) of 0.93. In addition, the two miRNAs were not only higher in moderate and severe MsPGN patients, but could distinguish MsPGN from MN. We also observed a decreased expression in MsPGN regression group after treatment. Plasma miR-106a-5p level was positively correlated with estimated glomerular filtration rate (eGFR). Furthermore, the two miRNAs were highly expressed in MsPGN glomerulus and their overexpression could prompt mesangial cell proliferation. Plasma miR-30a-5p and miR-106a-5p can serve as novel and potential diagnostic biomarkers for MsPGN. [ABSTRACT FROM AUTHOR]

Objective(s): Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS. Recent evidence indicates that Interleukin 17 (IL-17)- producing T helper cells (Th17 cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th17 and Treg differentiation, the role of microRNAs in MS is not completely understood. Thereby, as a step closer, we analyzed the expression profile of miR-9-5p and miR-106a-5p, and protein level of retinoic acid receptor (RAR)-related orphan receptor C (RORC; Th17 master transcription factor) as direct target of miR-106a-5p and forkhead box P3 (FOXP3; Treg master transcription factor) as indirect target of miR- 9-5p in CD4+ T cells in two groups of relapsing and remitting in our relapsing-remitting MS (RR-MS) patients. Materials and Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to assess the expression of miRNAs and mRNAs, in 40 RR-MS patients and 11 healthy individuals. Thus, FOXP3 and RAR-related orphan receptor κt (RORκt) was assessed in CD4+T-cells by flow cytometry. We also investigated the role of these miRNAs in Th17/Treg differentiation pathway through bioinformatics tools. Results: An up-regulation of miR-9-5p and down-regulation of miR-106a-5p in relapsing phase of MS patients were observed compared to healthy controls. RORC and FOXP3 were up-regulated in relapsing and remitting phases of MS, respectively. Conclusion: Expression pattern of miR-9-5p and miR-106a-5p and their targets suggest a possible inducing role of miR-9-5p and suppressing role of miR-106a-5p in differentiation pathway of Th17 cells during MS pathogenesis. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are aberrantly expressed in various cancers. Fer-1-like protein 4 (FER1L4), one of lncRNAs, plays a role as tumor suppressor in various human cancers and can be regulated by microRNA. However, the role and function of FER1L4 in human hepatocellular carcinoma (HCC) remains unknown. The aim of the present study was to annotate the role of FER1L4 and its clinical value in HCC. In the present study, we found that FER1L4 was lowly expressed in HCC tissue specimens as well as in malignant HCC cell lines, while the situation is opposite in miR-106a-5p. We found that down-regulated FER1L4 increased the expression of miR-106a-5p significantly and there was a reciprocal repression between FER1L4 and miR-106a-5p. Moreover, we identified FER1L4 as a target of miR-106a-5p by using dual-luciferase reporter assay. Knockdown of FER1L4 promoted the malignancy of HCC cells, including proliferation, migration, and invasion, and inhibited cell apoptosis. We also found that FER1L4 functions as a tumor suppressor in vivo. Together, these results suggest that FER1L4 could exert a tumor suppressive impact on HCC, which at least, in part, through suppressing miR-106a-5p expression. FER1L4, as well as miR-106a-5p, can predict the clinical prognosis of HCC alone or combined, which may be a novel therapeutic target for treating HCC. [ABSTRACT FROM AUTHOR]

The invasive behavior of glioblastoma multiforme (GBM) cells is an important reason for its poor prognosis. Tumor cells acquire an ability to digest the extracellular matrix and infiltrate the adjacent normal tissue during invasion. Restraining GBM invasion by changing effector molecules can significantly improve the patient's prognosis. MiRNAs are involved in multiple biological functions via suppressing target genes. In this study, we found that miR-106a-5p expression was high in GBM tissues and cells. The data showed an inverse correlation in GBM tissues between the levels of miR-106a-5p and adenomatosis polyposis coli (APC) mRNAs.Additionally, ectopic expression of miR-106a-5pfacilitated the invasion of GBM cells whereas inhibition of miR-106a-5p expression weakened the invasive ability. Numerous transcription factors are downstream effectors of the Wnt/β-catenin pathway. Target prediction databases and luciferase data showed that APC is a new direct target of miR-106a-5p. Importantly, westernblot assays demonstrated that miR-106a-5p can reduce APC protein level and enhance target proteins of Wnt/β-catenin pathway. Thus, we hypothesize that miR-106a-5p directly targets APC, resulting in the activation of Wnt/β-catenin pathway. Our results suggest that miR-106a-5p is involved in the invasive behavior of GBM cells and by targeting APC and activating Wnt/β-catenin pathway, it provides a theoretical basis for developing potential clinical strategies. [ABSTRACT FROM AUTHOR]

The microRNA (miR)-17 family is widely expressed in mammalian tissues and play important roles in various physiological and pathological processes. Here, the functions of miR-106a-5p, a member of miR-17 family, were explored during myogenic differentiation in C2C12 cell line. First, miR-106a-5p was found to be relatively lower expressed in two-month skeletal muscle tissues and gradually decreased upon myogenic stimuli. Forced expression of miR-106a-5p significantly reduced the differentiation index, fusion index as well as the expression of myogenic markers (MyoD, MyoG, MyHC, Myomixer, Myomarker). Meanwhile, the levels of phosphorylated AKT were reduced by overexpression of miR-106a-5p, and administration of insulin-like growth factor 1 (IGF1), a booster of myogenic differentiation, could recover all the inhibitory effects above of miR-106a-5p. Furthermore, miR-106a-5p was elevated in aged muscles and dexamethasone (DEX)-treated myotubes, and up-regulation of miR-106a-5p significantly reduced the diameters of myotubes accompanied with increased levels of muscular atrophy genes and decreased PI3K/AKT activities. Finally, miR-106a-5p was demonstrated to directly bind to the 3’-UTR of PIK3R1, thus, repress the PI3K/AKT signaling. [ABSTRACT FROM AUTHOR]

Background: Sex differences in the incidence and prognosis of respiratory diseases have been reported. Studies have shown that women are at increased risk of adverse health outcomes from air pollution than men, but sex-specific immune gene expression patterns and regulatory networks have not been well studied in the lung. MicroRNAs (miRNAs) are environmentally sensitive posttranscriptional regulators of gene expression that may mediate the damaging effects of inhaled pollutants in the lung, by altering the expression of innate immunity molecules. Methods: Male and female mice of the C57BL/6 background were exposed to 2 ppm of ozone or filtered air (control) for 3 h. Female mice were also exposed at different stages of the estrous cycle. Following exposure, lungs were harvested and total RNA was extracted. We used PCR arrays to study sex differences in the expression of 84 miRNAs predicted to target inflammatory and immune genes. Results: We identified differentially expressed miRNA signatures in the lungs of male vs. female exposed to ozone. In silico pathway analyses identified sex-specific biological networks affected by exposure to ozone that ranged from direct predicted gene targeting to complex interactions with multiple intermediates. We also identified differences in miRNA expression and predicted regulatory networks in females exposed to ozone at different estrous cycle stages. Conclusion: Our results indicate that both sex and hormonal status can influence lung miRNA expression in response to ozone exposure, indicating that sex-specific miRNA regulation of inflammatory gene expression could mediate differential pollution-induced health outcomes in men and women. [ABSTRACT FROM AUTHOR]