Differential expression of host oncogenes in human papillomavirus-associated nasopharyngeal and cervical epithelial cancers.

Human papillomavirus (HPV)-related cervical and nasopharyngeal cancers differ in molecular mechanisms underlying the oncogenic processes. The disparity may be attributed to differential expression of oncoproteins. The current study investigated the host oncogenes expression pattern in HPV-associated cervical and nasopharyngeal cancer. Formalin-fixed paraffin-embedded tissues originating from the nasopharyngeal and cervical regions were screened using Hematoxylin and Eosin staining. Genomic DNA and total RNA were extracted from confirmed cancer biopsies and non-cancer tissues (NC). HPV was detected by PCR using MY09/GP5+/6+ primers. Protein expression levels of AKT, IQGAP1, and MMP16 in HPV-infected cancers and controls were determined by immunohistochemistry. RT-qPCR was used to profile mRNAs of the oncogenes. AKT and IQGAP1 proteins were highly expressed in the epithelial cancers compared with the non-cancer tissues (p < 0.05). IQGAP1 and MMP16 mRNAs level was significantly higher in the cancers than in the NC (p < 0.05), but not AKT mRNA levels. MMP16 protein was ubiquitously expressed in all tissues. AKT mRNA level was significantly elevated in CC compared with NPC (p < 0.001). However, the difference in AKT, IQGAP1 and MMP16 proteins level between CC and NPC was not significant (p > 0.05). The oncoproteins expression level between the HPV-positive and HPV-negative cancer biopsies showed no significant difference (p < 0.05). Current study reports AKT but not IQGAP1 and MMP16 mRNAs differentially expression in cervical and nasopharyngeal cancers, independent of HPV infection status.

Astrocytoma with high-grade features and MYBL1-MMP16 fusion.

Background: Gliomas represent the most common primary intraparenchymal brain tumors in adult and pediatric patients. Neuropathological work-up of these gliomas typically entails the determination of isocitrate dehydrogenase (IDH) mutational status, presence or absence of 1p/19q co-deletion, and O6 methylguanine-DNA methyl-transferase (MGMT) promoter methylation status. Case Description: We present here an unusual case of a posterior fossa tumor in a 51-year-old female, which was initially diagnosed as astrocytoma with some high-grade features that recurred, displaying even more aggressive features such as infiltration and increased proliferative activity. Both the initially resected and recurrent tumor revealed MYBL1-MMP16 fusion, which is much more commonly found in pediatric low-grade gliomas and, to our knowledge has not been described in the context of an adult glioma. Conclusion: The significance of MYBL1-MMP16 fusion in adult gliomas in relation to survival and likelihood of recurrence is, therefore, unknown and requires more extensive research.

Circular RNA Circ_0122396 Regulates Human Lens Epithelial Cell Progression by Regulating miR-23a-3p and MMP16 in Age-Related Cataract.

BACKGROUND: CircRNA plays a regulatory role in multiple life processes. Circ_0122396 could participate in the regulation of age-related cataract (ARC) progression. However, the precise molecular mechanisms of circ_0122396 In ARC remain enigmatic. METHODS: Circ_0122396, microRNA (miR)-23a-3p, and matrix metalloprotease (MMP)-16 (MMP16) expression levels were detected via quantitative real-time polymerase chain reaction. Western blot was used to detect the levels of MMP16 and apoptosis-related proteins. Cell counting kit-8 analysis and 5-ethynyl-2'-deoxyuridine assay were used to assess human lens epithelial cells (HLECs) proliferation. Flow cytometry was performed to determine cell apoptosis. Levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were measured using commercial kits. Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were used to examine the interaction among circ_0122396, miR-23a-3p, and MMP16. RESULTS: Circ_0122396 and MMP16 were down-regulated while miR-23a-3p was up-regulated in ARC. H2O2 constrained proliferation and GSH-PX level, promotes apoptosis and MDA level in HLECs, and overexpression of circ_0122396 attenuated these effects. miR-23a-3p was a direct target of circ_0122396, and MMP16 was a direct target of miR-23a-3p. The effect of circ_0122396 overexpression on H2O2-induced HLECs was reversed by miR-23a-3p, and MMP16 elevation overturned the impacts of miR-23a-3p in H2O2-induced HLECs. CONCLUSIONS: Circ_0122396 may regulate the progression of ARC via the miR-23a-3p/MMP16 pathway in H2O2-stimulated HLECs, which may serve as a potentially valuable biomarker and novel therapeutic target for ARC.

Novel Approaches to Possible Targeted Therapies and Prophylaxis of Uterine Fibroids.

Uterine leiomyomas are the most common benign tumors in women of childbearing age. They may lead to problems of conception or complications during the gestational period. The methods of treatment include surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (ulipristal acetate, leuprolide acetate, cetrorelix, goserelin, mifepristone). Both approaches are efficient but incompatible with pregnancy planning. Therefore, there is a call for medical practice to develop therapeutical means of preventing leiomyoma onset in patients planning on becoming pregnant. Based on the analysis of GWAS data on the search for mononucleotide polymorphisms associated with the risk of leiomyoma, in meta-transcriptomic and meta-methylomic studies, target proteins have been proposed. Prospective therapeutic treatments of leiomyoma may be based on chemical compounds, humanized recombinant antibodies, vaccines based on markers of the uterine leiomyoma cells that are absent in the adult organism, or DNA and RNA preparations. Three different nosological forms of the disease associated with driver mutations in the MED12, HMGA2, and FH genes should be considered when developing or prescribing drugs. For example, synthetic inhibitors and vaccines based on matrix metalloproteinases MMP11 and MMP16 are expected to be effective only for the prevention of the occurrence of MED12-dependent nodules.

MMP16 as NSCL ± P Susceptible Gene in Western Han Chinese.

OBJECTIVE: The role of MMP16 in lip development is unclear. This study aimed to identify nonsyndromic cleft lip with or without palate (NSCL ± P) susceptible loci of MMP16 in western Han Chinese. DESIGN: We performed targeted sequencing around MMP16 combined with a 2-phase association analysis on common variants. Phase 2 association analysis was performed with NSCL ± P specific subphenotypes (NSCL and NSCLP). Then we used rare variants burden analysis and genotyping, accompanied by motif analysis. SETTING: This study was completed in a tertiary medical center. PATIENTS, PARTICIPANTS: Phase 1 targeted sequencing included 159 patients with NSCL ± P and 542 normal controls; phase 2 included 1626 patients with NSCL ± P (1047 NSCL and 579 NSCLP) and 2255 normal controls. INTERVENTIONS: Venous blood samples were collected from patients and used to extract DNA. MAIN OUTCOME MEASURES: After Bonferroni correction, phase 1 significant threshold of p-value was 4.28 × 10-5 (0.05/1167 single nucleotide polymorphisms [SNPs]), and phase 2 was .00025 (0.05/200 SNPs). Burden analysis significant threshold p-value was .05. RESULTS: Common variants phase 1 association analysis identified 11 statistically significant SNPs (lowest p = 1.90 × 10-9, odds ratio (OR) = 0.27, 95% CI: 0.17-0.44), phase 2 replication identified 16 SNPs in NSCL ± P (lowest p = 6.26 × 10-6, OR = 0.77, 95% CI: 0.69-0.86) and 9 in NSCL (lowest p = 8.44 × 10-5, OR = 0.76, 95% CI: 0.66-0.87). Rare variants burden analysis showed no significant results, genotyping results showed they were maternally inherited. CONCLUSIONS: Our study identified MMP16 susceptible SNPs in NSCL ± P and NSCL, emphasizing its potential role in lip development. Our study also highlighted the importance to perform association analysis with subphenotypes divided.

Tumor Cell-Derived Exosomal Circ-0072088 Suppresses Migration and Invasion of Hepatic Carcinoma Cells Through Regulating MMP-16.

Background: Tumor-derived exosomes (EXOs), commonly differentially expressed in circular RNAs, have been shown to be crucial determinants of tumor progression and may regulate the development and metastasis of hepatic carcinoma (HCC). Methods: Possibly differentially expressed circRNAs in patients with HCC were screened out from the Gene Expression Omnibus (GEO). EXOs were isolated from the culture medium of HCC cells and plasma of patients with HCC, followed by characterization by transmission electron microscope, NanHCCight, and western blotting. Additionally, RNA immunoprecipitation and luciferase reporter gene assays were carried out to explore the molecular mechanism of hsa_circRNA_103809 (circ-0072088) in HCC cells. Results: The screening results showed that circ-0072088 was highly expressed in patients with HCC, and its increase indicated unfavorable prognosis of patients according to quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Additionally, circ-0072088 was mainly secreted by HCC cells via EXOs in plasma of such patients, and its high level in plasma EXOs was closely associated with tumor node metastasis (TNM) staging and tumor size. Moreover, HCC-secreted EXOs mediated the degradation of miR-375 via circ-0072088 and upregulated MMP-16, thus suppressing the metastasis of HCC. Conclusion: Upregulated in patients with HCC, circ-0072088 may be an index for diagnosis and prognosis of HCC. In addition, HCC-derived EXOs coated with circ-0072088 might be a treatment for HCC, with the ability to inhibit the metastasis of HCC cells.

LncRNA NEAT1 regulates MMP-16 by targeting miR-200a/b to aggravate inflammation in asthma.

Asthma is a common respiratory disease which is characterized by persistent airway inflammation. Abnormal expression of long non-coding RNAs (lncRNAs) is observed in asthma. However, whether lncRNA nuclear-enriched abundant transcript 1 (NEAT1) regulates asthmatic inflammation and its mechanism still needs to be further investigated. The expression levels of inflammatory factors (tumour necrosis factor (TNF)-α, interleukin (IL)-4, IL-13, and IL-10) were detected using reverse transcription quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). MTT and flow cytometry assays were employed to determine cell proliferation and apoptosis, respectively. Dual luciferase reporter assay was performed to verify the relationship between miR-200a/b and MMP-16 or NEAT1. NEAT1 silencing markedly reduced TNF-α, IL-4, and IL-13 levels, while elevated IL-10 expression, suppressed cell proliferation, and promoted cell apoptosis. However, NEAT1 overexpression elicited the opposite effects on cell proliferation and inflammation cytokines secretion. What is more, NEAT1 negatively regulated miR-200a/b expression, and MMP16 was a target gene of miR-200a/b. miR-200a/b overexpression suppressed inflammation, cell proliferation, and enhanced cell apoptosis through regulation of MMP16. Moreover, MMP-16 overexpression or miR-200a/b inhibition abolished the regulatory effect of sh-NEAT1 on cell inflammation and apoptosis in BEAS-2B cells. NEAT1 acted as the role of sponge for miR-200a/b to regulate MMP-16 expression, thereby promoting asthma progression, suggesting that NEAT1 might have great potential as therapeutic target for asthma.

Silencing of circHIPK3 hampers platelet-derived growth factor-induced proliferation and migration in airway smooth muscle cells through the miR-375/MMP-16 axis.

Emerging evidence has suggested a pivotal role of circular RNAs (circRNAs) in the progression of asthma. In this paper, we explored the mechanisms underlying the modulation of circRNA homeodomain interacting protein kinase 3 (circHIPK3, circ_0000284) in airway smooth muscle cell (AMSC) migration and proliferation induced by platelet-derived growth factor (PDGF). The stability of circHIPK3 was gauged by Ribonuclease R (RNase R) and Actinomycin D assays. Relative expression levels of circHIPK3, microRNA (miR)-375 and matrix metallopeptidase 16 (MMP-16) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, invasion, and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay, transwell assay, and flow cytometry, respectively. Cell migration was detected by wound-healing and transwell assays. Direct relationship between miR-375 and circHIPK3 or MMP-16 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Our results indicated that PDGF induced the expression of circHIPK3 in human AMSCs (HAMSCs). CircHIPK3 silencing impeded proliferation, migration, invasion and promoted apoptosis of PDGF-treated HAMSCs. Mechanistically, circHIPK3 targeted miR-375 by directly binding to miR-375. MiR-375 was a downstream effector of circHIPK3 in controlling PDGF-induced proliferation, invasion and migration. MMP-16 was directly targeted and inhibited by miR-375, and circHIPK3 functioned as a post-transcriptional modulator of MMP-16 expression through miR-375. Moreover, miR-375-mediated inhibition of MMP-16 impacted HAMSC proliferation, invasion and migration induced by PDGF. Our findings identified the miR-375/MMP-16 axis as a novel mechanism for the modulation of circHIPK3 in PDGF-induced migration and proliferation in HASMCs.

Menopause, Ultraviolet Exposure, and Low Water Intake Potentially Interact with the Genetic Variants Related to Collagen Metabolism Involved in Skin Wrinkle Risk in Middle-Aged Women.

Genetic and environmental factors influence wrinkle development. We evaluated the polygenetic risk score (PRS) by pooling the selected single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) for wrinkles and the interaction of PRS with lifestyle factors in middle-aged women. Under the supervision of a dermatologist, the skin status of 128 women aged over 40 years old was evaluated with Mark-Vu, a skin diagnosis system. PRS was generated from the selected SNPs for wrinkle risk from the genome-wide association study. Lifestyle interactions with PRS were also evaluated for wrinkle risk. Participants in the wrinkled group were more likely to be post-menopausal, eat less fruit, take fewer vitamin supplements, exercise less, and be more tired after awakening in the morning than those in the less-wrinkled group. The PRS included EGFR_rs1861003, MMP16_rs6469206, and COL17A1_rs805698. Subjects with high PRS had a wrinkle risk 15.39-fold higher than those with low PRS after adjusting for covariates, and they had a 10.64-fold higher risk of a large skin pore size. Menopause, UV exposure, and water intake interacted with PRS for wrinkle risk: the participants with high PRS had a much higher incidence of wrinkle risk than those with low PRS, only among post-menopausal women and those with UV exposure. Only with low water intake did the participants with medium PRS have increased wrinkle risk. In conclusion, women aged >40 years with high PRS-related collagen metabolism may possibly avoid wrinkle risk by avoiding UV exposure by applying sunscreen, maintaining sufficient water intake, and managing estrogen deficiency.

MicroRNA-377-3p targeting MMP-16 inhibits ovarian cancer cell growth, invasion, and interstitial transition.

BACKGROUND: To evaluate role of microRNA (miRNA)-377-3p on the remission of ovarian cancer (OC) cell proliferation, invasion, and interstitial transition in vivo and vitro. METHODS: SKOV3 cells were used as the object of in vitro research and four-week-old immunodeficient BABL/c female nude mice were used to form the xenograft model. Cell models were constructed by transfecting NC mimics, miR-377 mimic, plasmid cloning DNA (pcDNA), pc-matrix metalloproteinase (MMP)-16, or co-transfecting miR-377 mimic and pc-MMP-16. TargetScan software was used to predict the targeting relationship between miRNA-377-3p and MMP-16 in OC cells. The combination of miRNA-377-3p and MMP-16 was detected by dual luciferase report experiment. miRNA expression levels of miRNA-377-3p and MMP-16 in each transfection group cells were detected by reverse transcription-polymerase chain reaction (RT-PCR). The proliferation of SKOV3 cells were assessed by 5-ethynyl-2'-deoxyuridine (EdU) staining and microtubule formation, while the invasion ability of SKOV3 cells was detected by Transwell assay. Protein expression levels of MMP-16, survivin, Ki67, vascular endothelial growth factor (VEGF), E-cadherin, and N-cadherin were detected by Western blot (WB), and the positive cells of Ki67 and VEGF were detected by immunohistochemistry (IHC). RESULTS: MMP-16 overexpression markedly increased the EDU-positive cell percentage, upregulated survivin and Ki67 levels, increased the number of invasive cells per field, and enhanced VEGF and N-cadherin expression. Importantly, co-transfection of miRNA-377-3p and MMP-16 reversed these abnormal phenomena. Xenotransplantation mouse models were formed by injecting SKOV-3 cells subcutaneously. Tumor size, tumor volume, and tumor weight were all reduced in the miR-377-3p mimic-transfected group. The results of IHC indicated that Ki67 and VEGF expression were decreased in the miR-377-3p mimic-transfected group. CONCLUSIONS: These findings indicate that miR-377-3p could be a promising therapeutic agent for OC cell growth, invasion, and interstitial transition with MMP-16 being its likely target.

Berberine inhibited metastasis through miR-145/MMP16 axis in vitro.

Ovarian cancer is the first leading cause of death in gynecological cancers. The continuous survival and metastasis of cancer cells are the main causes of death and poor prognosis in patients with ovarian cancer. Berberine is an effective component extracted from the rhizomes of coptis chinensis and phellodendron chinensis. In our study, we aim to explore the molecular mechanism underlying the regulation of proliferation, migration and invasion by berberine in ovarian cancer cells. CCK8 assay was used for detection of proliferative capacity of SKOV3 and 3AO cells. Wound healing assay was used to estimate cell migration and transwell assay was used to assess cell invasion. The mRNA expression of miR-145 and MMP16 were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The protein level of MMP16 was detected by western blot analysis. In addition, luciferase reporter assays were used to demonstrate MMP16 was a target of miR-145. The results demonstrated berberine inhibited proliferation, migration and invasion, promoted miR-145 expression, and decreased MMP16 expression in SKOV3 and 3AO cells. MMP16 was a target of miR-145. Moreover, downregulation of MMP16 contributed to the inhibition of proliferation, migration and invasion by berberine. Together, our results revealed that berberine inhibited proliferation, migration and invasion through miR-145/MMP16 in SKOV3 and 3AO cells, highlighting the potentiality of berberine to be used as a therapeutic agent for ovarian cancer.

Association between MMP16 rs60298754 and clinical phenotypes of Parkinson's disease in southern Chinese.

STUDY OBJECTIVES: The aim was to investigate the association between MMP16 rs60298754 and symptoms of Parkinson's disease (PD) in southern Chinese. METHODS: Seven hundred forty-five PD patients were recruited in this study. All patients were evaluated by Brief Pain Inventory (BPI), Hamilton anxiety rating scale and Hamilton depression rating scale, 39-item Parkinson's disease Questionnaire (PDQ-39), and MDS-Unified PD Rating Scale (MDS-UPDRS). Symptoms were also recorded. RESULTS: The difference of BPI and Parkinson's disease sleep scale (PDSS) between two groups was showed (BPI: MMP16 wildtypes: 14.73 ± 14.45; MMP16 carriers: 10.95 ± 10.67, p 0.002; PDSS: MMP16 wildtypes: 117.80 ± 21.45; MMP16 carriers: 108.40 ± 23.95, p < 0.001). The association of apathy, nocturia, and sensitive to light were found (apathy: p 0.001, OR: 0.49, 0.32-0.76; nocturia: p < 0.001, OR: 3.57, 1.90-7.26; sensitive to light: p < 0.001, OR: 3.99, 2.01-7.74). CONCLUSIONS: MMP16 rs60298754 was associated with the presence of apathy, pain, nocturia, and sensitive to light.

CircRNA has_circ_0001806 promotes hepatocellular carcinoma progression via the miR-193a-5p/MMP16 pathway

Reportedly, circular RNAs (circRNAs) are crucial regulators in cancer progression. Nonetheless, the molecular mechanism of circRNAs in hepatocellular carcinoma (HCC) has not been fully clarified. Gene expression omnibus (GEO) database was employed to screen out the differentially expressed circRNAs in HCC. qRT-PCR and western blot were executed to detect circ_0001806 expression, miR-193a-5p expression, and MMP16 mRNA and protein expressions in HCC. The effect of circ_0001806 on HCC was analyzed by the CCK-8 method and Transwell experiment. RIP assay, pull-down experiment, and dual-luciferase reporter gene experiment were applied to validate the targeting relationships among circ_0001806, miR-193a-5p, and MMP16. Circ_0001806 was up-modulated in HCC tissues and cell lines. Knockdown of circ_0001806 impeded the multiplication, migration, and invasion of HCC cells. Circ_0001806 could up-regulate MMP16 expression through repressing miR-193a-5p, thereby facilitating the malignant biological behaviors of HCC. Circ_0001806 promoted HCC progression by regulating miR-193a-5p/MMP16 axis.

microRNA-26a Directly Targeting MMP14 and MMP16 Inhibits the Cancer Cell Proliferation, Migration and Invasion in Cutaneous Squamous Cell Carcinoma.

PURPOSE: To investigate the specific effect and underlying mechanism of microRNA-26a-5p (miR-26a) in cutaneous squamous cell carcinoma (CSCC). METHODS: miR-26a and MMP14/16 mRNA expression were detected by qRT-PCR analysis. Functional experiments were used to detect the role of miR-26a on CSCC progression. Western blot was used for protein detection. Luciferase assay was used to detect miR-26a directly targeting MMP14 and MMP16. Xenograft nude mice model was used to determine the effect of miR-26a on tumorigenesis. RESULTS: miR-26a was decreased in CSCC tissues and cells. Forced miR-26a suppressed the progression of SCL-1 and A431 cells. Furthermore, miR-26a directly targeted MMP14 and MMP16 to inhibit their expression. Forced expression of MMP14 and MMP16 removed the miR-26a's inhibitory effect on CSCC development. The in vivo tumor growth assay showed that miR-26a suppressed CSCC tumorigenesis by targeting MMP14 and MMP16. CONCLUSION: Our study suggested miR-26a inhibits cancer cell proliferation, migration and invasion in CSCC by targeting MMP14 and MMP16.

LINC01121 induced intervertebral disc degeneration via modulating miR-150-5p/MMP16 axis.

BACKGROUND: Growing evidence indicates that Long noncoding RNAs contribute to cell differentiation, invasion, metabolism, proliferation and metastasis. However, the potential role of LINC01121 in progression of intervertebral disc degeneration (IDD) remains unclear. METHODS: LINC01121, matrix metalloprotease (MMP)-16 and miR-150-5p expression was determined by a quantitative-reverse transcriptase-polymerase chain reaction assay. Inflammatory cytokines level was measured by an enzyme-linked immunosorbent assay and cell counting kit-8 analysis was used to assess cell proliferation. MMP-16-specific binding with miR-150-5p was verified with a luciferase reporter assay. RESULTS: We noted that interleukin (IL)-1ß and tumor necrosis factor (TNF)-α treatment enhanced LINC01121 and MMP-16 expression in nucleus pulposus (NP) cells. LINC01121 was higher in IDD specimens compared to that in control specimens. Higher expression of LINC01121 was correlated with disc degeneration degree. Ectopic expression of LINC01121 enhanced cell proliferation and promoted ki-67, MMP-3 and ADAMTS5 expression and also suppressed collagen II expression in NP cells. We observed that overexpression of LINC01121 increased the secretion of three inflammatory cytokines, including IL-6, TNF-α and IL-1ß. We found that ectopic expression of LINC01121 decreased the miR-150-5p level in NP cells. Luciferase reporter data confirmed that MMP-16 was one direct target of miR-150-5p. Overexpression of miR-150-5p inhibited MMP-16 level and elevated the expression of LINC01121 enhanced MMP-16 level. We also found that MMP-16 was up-regulated in IDD specimens compared to that in control specimens. Higher expression of MMP-16 was correlated with disc degeneration degree. Interestingly, MMP-16 expression was positively related to LINC01121 in IDD specimens. Finally, overexpression of LINC01121 regulated cell growth, extracellular matrix degradation and inflammatory cytokine secretion via modulating MMP-16. CONCLUSIONS: our data suggested LINC01121 may be a new therapeutic target for IDD.

A protective polymorphism in MMP16, improved blood gas levels, and chronic obstructive pulmonary diseases: Family and two population-based studies.

The aberrant expression of matrix metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary disease (COPD). In the discovery stage, 11 COPD from five families were subjected to whole-genome sequencing, and 21 common polymorphisms in MMPs and TIMPs were identified. These polymorphisms were genotyped in two subsequent verification studies. Of these polymorphisms, c.2392G>A (rs2664370T>C) and c.4158C>A (rs2664369T>G) in MMP16 remained significantly different. Functionally, we found that MMP16 expression was significantly increased in peripheral blood monocytes (PBMCs) from COPD and in cigarette smoke extract-treated 16HBE cells compared with controls. This was also shown by bioinformatics analysis. COPD carrying rs2664370CC showed decreased levels of MMP16 in the plasma and in PBMCs compared with those carrying CT and TT. Treatment with hsa-miR-576-5p mimics led to a greater reduction in luciferase reporter activity in cells transfected with rs2664370CC. Moreover, blood levels of base excess, PCO2 , and PO2 in COPD with rs2664370CC were significantly lower than those with rs2664370CT+TT. Taken together, these results demonstrate that the rs2664370T>C polymorphism in MMP16 protects against the risk of COPD, likely by favoring interaction with hsa-miR-576-5p, leading to reduced MMP16 expression and improved blood gas levels.

Association of Gene Polymorphism of Bactericidal Permeability Increasing Protein Rs4358188, Cluster of Differentiation 14 Rs2569190, Interleukin 1ß Rs1143643 and Matrix Metalloproteinase-16 Rs2664349 with Neonatal Sepsis.

BACKGROUND: Neonatal sepsis is a health problem because it causes serious morbidity and mortality in neonate intensive care units. The susceptibility of neonates occurs due to the immaturity of immune system development as well as due to maternal and environmental risk factors that can cause infection. Identification of genetic variation in genes involved in the inflammatory process can help clarify the pathophysiology of sepsis in high-risk patients, useful for the development of new diagnostic tools, and specific management plans for more accurate predictions of patient's prognosis. AIM: This study aims to determine the association between gene polymorphism of BPI rs4358188, CD14 rs2569190, IL1ß rs1143643 or MMP16 rs2664349 and the incidence of neonatal sepsis. METHODS: Cross-sectional observational studies with genomic DNA samples from infants with sepsis and non-sepsis which were stored according to the standard storage of genetic materials in the Biomedical Laboratory of Faculty of Medicine Universitas Andalas Padang City, Indonesia. This study is part of a previous study by Rukmono P. Continued with PCR examination, sequencing and bioinformatics analysis. RESULTS: Only IL1ß rs1143643 G > A gene polymorphism was associated with the incidence of neonatal sepsis and was statistically significant (p = 0.017). No significant association was found between gene polymorphisms of BPI rs4358188 G > T, CD14 rs2569190 A>G or MMP16 rs2664349 G > A and neonatal sepsis (p > 0.05). CONCLUSION: Gene polymorphism of IL1ß rs1143643 G > A is associated with the incidence of neonatal sepsis.

Sevoflurane suppresses migration and invasion of glioma cells by regulating miR-146b-5p and MMP16.

Background: Glioma is the most common brain tumor with poor prognosis all over the world. Anesthetics have been demonstrated to have important impacts on cell migration and invasion in different cancers. However, the underlying mechanism that allows anesthetics-mediated progression of glioma cells remains elusive. Methods: Sevoflurane (Sev), a class of common anesthetics, was used to expose to U87-MG and U251 cells. The expressions of microRNA-146b-5p (miR-146b-5p) and matrix metallopeptidase 16 (MMP16)were measured by quantitative real-time polymerase chain reaction or western blot. Transfection was performed in glioma cells with miR-146b-5p inhibitor, inhibitor negative control, MMP16 overexpression vector, empty vector, small interfering RNA against MMP16 or scramble. Cell migration and invasion were analyzed by the trans-well assay. The interaction between miR-146b-5p and MMP16 was explored by luciferase activity and RNA immunoprecipitation assays. Results: Sev treatment inhibited migration and invasion of glioma cells. The expression of miR-146b-5p was enhanced and MMP16 protein was decreased in glioma cells after exposure of Sev. Knockdown of miR-146b-5p or overexpression of MMP16 reversed Sev-induced inhibition of migration and invasion of glioma cells. Moreover, MMP16 was indicated as a target of miR-146b-5p and its silencing attenuated the regulatory role of miR-146b-5p abrogationin Sev-treated glioma cells. Conclusion: Sev impeded cell migration and invasion through regulating miR-146b-5p and MMP16 in glioma, indicating a novel theories foundation for the application of anesthetics like Sev in glioma.

Rosmarinic inhibits cell proliferation, invasion and migration via up-regulating miR-506 and suppressing MMP2/16 expression in pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer-related deaths worldwide. However, therapeutic strategies for the treatment of pancreatic cancer are still limited. Therefore, it is urgent for us to develop novel effective therapies for pancreatic cancer. In this study, we explored the effects of rosmarinic acid on pancreatic progression and explored the underlying molecular mechanisms. Rosmarinic acid significantly suppressed cell viability, cell growth, cell invasion and migration as well as epithelial mesenchymal transition (EMT) of pancreatic cancer cells, and induced cell apoptosis in pancreatic cells. In addition, rosmarinic acid significantly up-regulated the expression of miR-506 in pancreatic cancer cells, and knockdown of miR-506 attenuated the suppressive effects of rosmarinic acid on cell growth, cell invasion and migration and EMT, and prevented the enhanced effects of rosmarinic acid on cell apoptosis in pancreatic cancer cells. Mechanistically, the luciferase reporter assay showed that miR-506 targeted the 3' untranslated region of matrix metalloproteinase (MMP)-2/16, and miR-506 overexpression and rosmarinic acid treatment suppressed the expression of MMP2/16 in pancreatic cancer cells. Overexpression of MMP2/16 attenuated the inhibitory effects of rosmarinic acid on pancreatic cell invasion and migration. In vivo studies showed that rosmarinic acid dose-dependently suppressed tumor growth of pancreatic cancer cells, and increased the expression of miR-506, while suppressed the expression of MMP2/16 and Ki-67 in dissected tumor tissues from xenograft nude mice. Collectively, our results for the first time revealed the anti-tumor effects of rosmarinic acid in pancreatic cancer, and the anti-tumor effects of rosmarinic acid were via regulating the miR-506/MMP2/16 axis in pancreatic cancer.