Role Of miR-210 Research Articles

MiR-195 Inhibits EMT by Targeting FGF2 in Prostate Cancer Cells.

Prostate cancer (PCa) is one of the leading causes of deaths in America. The major cause of mortality can be attributed to metastasis. Cancer metastasis involves sequential and interrelated events. miRNAs and epithelial-mesenchymal transition (EMT) are implicated in this process. miR-195 is downregulated in many human cancers. However, the roles of miR-195 in PCa metastasis and EMT remain unclear. In this study, data from Memorial Sloan Kettering Cancer Center (MSKCC) prostate cancer database were re-analysed to detect miR-195 expression and its roles in PCa. miR-195 was then overexpressed in castration-resistant PCa cell lines, DU-145 and PC-3. The role of miR-195 in migration and invasion in vitro was also investigated, and common markers in EMT were evaluated through Western blot analysis. A luciferase reporter assay was conducted to confirm the target gene of miR-195; were validated in PCa cells. In MSKCC data re-analyses, miR-195 was poorly expressed in metastatic PCa; miR-195 could be used to diagnose metastatic PCa by measuring the corresponding expression. Area under the receiver operating characteristic curve (AUC-ROC) was 0.705 (P = 0.017). Low miR-195 expression was characterised with a shorter relapse-free survival (RFS) time. miR-195 overexpression suppressed cell migration, invasion and EMT. Fibroblast growth factor 2 (FGF2) was confirmed as a direct target of miR-195. FGF2 knockdown also suppressed migration, invasion and EMT; by contrast, increased FGF2 partially reversed the suppressive effect of miR-195. And data from ONCOMINE prostate cancer database showed that PCa patients with high FGF2 expression showed shorter RFS time (P = 0.046). Overall, this study demonstrated that miR-195 suppressed PCa cell metastasis by downregulating FGF2. miR-195 restoration may be considered as a new therapeutic method to treat metastatic PCa.

Abstract 16449: miR-195 Regulates Myocardial SIRT3 Expression and Mitochondrial Enzyme Acetylation

Background: Unique cardiac and systemic miRNAs play an important role in cardiac remodeling and the associated response to injury by modulating key signaling elements. Through deep-sequencing of cardiac and circulating non-coding miRNAs, we identified miR-195 as the only miRNA up-regulated in plasma, serum and myocardium of patients with advanced heart failure (HF). Further, binding elements for miR-195 were found in the 3’UTR region of sirtuin3 (SIRT3), the major mitochondrial deacetylase. We hypothesized that miR-195 regulates myocardial SIRT3 expression and mitochondrial protein acetylation levels with subsequent changes in cardiac metabolism. Methods: Cellular signaling was analyzed in human cardiomyocyte-like AC16 cells and acetylation levels in a rodent model of transgenic miR-195 overexpression were compared to WT. Luciferase assays, Western blotting and immunoprecipitation (Co-IP) assays were performed. Enzymatic activities of pyruvate dehydrogenase (PDH) and ATP synthase were measured. Results: We observed suppression of SIRT3 and increased total protein acetylation in failing human myocardium. Luciferase assays confirmed that miR-195 directly targets the SIRT3 mRNA 3’UTR and negatively regulates SIRT3 expression. Transfection of miR-195 into AC16 cells resulted in a pronounced decrease in SIRT3 expression levels and induction of total protein acetylation levels. Myocardium of miR-195 transgenic animals was showed a global increase in total protein acetylation compared to WT. Co-IP assays revealed increased acetylation of 3 subunits of PDH (2.1-, 1.6-, 2.2-fold) and ATP synthase α subunit (2.3-fold), two key regulators of mitochondrial energy metabolism. Enhanced acetylation of these proteins correlated with a 24% decrease in PDH activity and a 30% decrease in ATP synthase activity. Conclusions: Altogether, these data demonstrate a crucial role of miR-195 in HF and identified SIRT3 as a direct target of miR-195. Our findings suggest a new pathway of abnormal cardiac energy metabolism in the failing myocardium through miR-195-mediated SIRT3 suppression and increased protein acetylation. These changes result in specific inhibition of PDH and ATP synthase activity leading to impaired energy metabolism and ATP deprivation.

Role of miR-138 in the regulation of larynx carcinoma cell metastases.

The cases of larynx carcinoma (LC) with poor prognosis largely result from the distal metastases of the primary tumor. Since microRNAs (miRNAs) play critical roles during cancer metastases, determination of the involved miRNAs in the regulation of the LC metastases may provide novel therapeutic targets for LC treatment. Here, we studied the LC specimens from the patients and found that the levels of miR-138 were significantly decreased and the levels of ZEB2, a critical factor that regulates cancer cell invasiveness, were significantly increased in LC, compared to the paired normal larynx tissue. Metastatic LC appeared to contained lower levels of miR-138. Moreover, miR-138 and ZEB2 inversely correlated in LC specimens. Bioinformatics analyses showed that miR-138 targeted the 3'-untranslated region (3'-UTR) of ZEB2 mRNA to inhibit its translation, which was confirmed in a luciferase reporter assay. Further, miR-138 overexpression inhibited ZEB2-mediated cell invasiveness, while miR-138 depletion increased ZEB2-mediated cell invasiveness in LC cells. Together, our data suggest that miR-138 suppression in LC cells may promote ZEB2-mediated cancer metastases. Thus, miR-138 appears to be an intriguing therapeutic target to prevent metastases of LC.

Role of miR-182 in response to oxidative stress in the cell fate of human fallopian tube epithelial cells.

High grade serous ovarian carcinoma (HGSC) is a DNA instable tumor and its precursor is commonly found originating from the fimbriated end of the fallopian tube secretory epithelial (FTSE) cells. The local stresses via ovulation and related inflammation are risks for HGSC. In this study, we examined the cellular and molecular responses of FTSE cells to stress. We found that excess intracellular reactive oxygen species (ROS) in normal FTSE cells upregulated a subset of microRNA expression (defined as ROSmiRs). Most ROSmiRs' expression and function were influenced and regulated by p53, and together they drove the cells into stress-induced premature senescence (SIPS). However, ROS-induced miR-182 is regulated by β-catenin, not by p53. In normal FTSE cells, miR-182 overexpression triggers cellular senescence by p53-mediated upregulation of p21. Conversely, in cells with p53 mutations, miR-182 overexpression no longer enhances p21 but functions as an "Onco-miR". p53 dysfunction is a prerequisite for miR-182-mediated tumorigenesis. In addition, we found that human follicular fluid could significantly induce intracellular ROS in normal FTSE cells. These findings suggest that ROS and p53 mutations may trigger a series of events, beginning with overexpressing miR-182 by ROS and β-catenin, impairing the DNA damage response, promoting DNA instability, bypassing senescence and eventually leading to DNA instable tumors in FTSE cells.

GW26-e4640 A critical role of miR-195 in pressure overload-induced cardiac remodeling

GW26-e4640 A critical role of miR-195 in pressure overload-induced cardiac remodeling

MicroRNA-9 regulates osteoblast differentiation and angiogenesis via the AMPK signaling pathway.

MiR-9 has been found to be involved in the repair of spinal cord injury and regulates the proliferation and differentiation of mesenchymal stem cells. However, the role of miR-9 in repair of bone defects has not been well studied. The current study was designed to investigate its role and potential underlying mechanism in regulating osteoblast differentiation and angiogenesis. After treating the murine pre-osteoblast cell line MC3T3-E1 with BMP2, miR-9 expression was obviously down-regulated. Following transfection with miR-9 mimics, its overexpression enhanced the differentiation of MC3T3-E1 cells into osteoblasts as evidence that miR-9 up-regulated the mRNA levels of osteoblast differentiation-related protein, as well as increased differentiation and mineralization of osteoblasts. Further functional analysis has shown that miR-9 overexpression effectively increased human umbilical vein endothelial cell proliferation. Moreover, miR-9 up-regulation promoted cell migration, VEGF, and VE-cadherin concentrations, as well as tube formation in vitro. The mechanistic assay demonstrated that overexpression of miR-9-induced activation of the AMPK signaling pathway. Taken together, our findings suggested that miR-9 overexpression promoted osteoblast differentiation and angiogenesis via the AMPK signaling pathway, representing a novel and potential therapeutic target for the treatment of bone injury-related diseases.

Role of miR-140 in embryonic bone development and cancer.

Bone is increasingly viewed as an endocrine organ with key biological functions. The skeleton produces hormones and cytokines, such as FGF23 and osteocalcin, which regulate an extensive list of homoeostatic functions. Some of these functions include glucose metabolism, male fertility, blood cell production and calcium/phosphate metabolism. Many of the genes regulating these functions are specific to bone cells. Some of these genes can be wrongly expressed by other malfunctioning cells, driving the generation of disease. The miRNAs are a class of non-coding RNA molecules that are powerful regulators of gene expression by suppressing and fine-tuning target mRNAs. Expression of one such miRNA, miR-140, is ubiquitous in chondrocyte cells during embryonic bone development. Activity in cells found in the adult breast, colon and lung tissue can silence genes required for tumour suppression. The realization that the same miRNA can be both normal and detrimental, depending on the cell, tissue and time point, provides a captivating twist to the study of whole-organism functional genomics. With the recent interest in miRNAs in bone biology and RNA-based therapeutics on the horizon, we present a review on the role of miR-140 in the molecular events that govern bone formation in the embryo. Cellular pathways involving miR-140 may be reactivated or inhibited when treating skeletal injury or disorder in adulthood. These pathways may also provide a novel model system when studying cancer biology of other cells and tissues.

Abstract 3078: Epigenetic regulation of miR-138 confers cancer stem cell characteristics of renal cell carcinoma

Abstract Chemotherapy is the standard care for metastatic disease, in renal cell carcinoma (RCC), the outcome of chemotherapy only prolongs short survival of patients. The reason for the resistance of RCC to chemotherapy is not fully understood, although it has been speculated that overabundance of ATP-binding cassette (ABC)/p-glycoprotein transporter system in RCC might be the reason to repel various chemotherapeutic agents away from the cancer cell. Meanwhile, cancer stem cells (CSC) theory has also focused a significant attention in recent years as a potential explanation for drug resistance and metastasis of RCC. In this study, we demonstrate that drug resistant RCC cells exhibit CSC phenotypes and miR-138 that is significantly downregulated in RCC acted critical role in suppressing CSC phenotype by targeting ABC transporter ABCA13 and oncogenic histone methyltransferase EZH2. Importantly, miR-138 levels were significantly enhanced by treatment of DNA hypomethylating agent (i.e., 5-aza) or histone deactylases inhibitor (i.e., TSA). Epigenetic silencing of tumor-suppressive micro-RNAs has been shown a key oncogenic mechanism for the activation of oncogenes in tumors. Indeed, depletion of miR-138 promoted CSC phenotype followed by enhanced expressions of ABCA13 and EZH2. Furthermore, a novel tumor suppressor DAB2IP can inhibit DNA methyltransferase 1 (DNMT1) activity, which results in miR-138 expression. Taken together, this study identifies the new role of miR-138 in RCC-CSC and unveils a unique regulation of tumor suppressor protein in DNMT1. Overall study provides not only a new biomarker of RCC-CSC and but also potential therapeutic strategy of targeting drug resistant RCC. Citation Format: Eun-Jin Yun, Jiancheng Zhou, Chun-Jung Lin, Elizabeth Hernandez, John Santoyo, Jer-Tsong Hsieh. Epigenetic regulation of miR-138 confers cancer stem cell characteristics of renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3078. doi:10.1158/1538-7445.AM2015-3078

Role of miR210 in hypoxia-induced mitochondrial dysfunction in placenta with preeclampsia

Role of miR210 in hypoxia-induced mitochondrial dysfunction in placenta with preeclampsia

The expression and role of miR-195 in diabetic retinopathy

Objective To investigate the expression of miR-195 and the underlying molecular mechanisms of miR-195 regulating HMGB1 in diabetic retinopathy (DR). Methods Extract 5 ml venous blood from DR patients, diabetes mellitus (DM) patients and normal subjects, then extract and perificate plasma total RNA. MicroRNA array and real time polymerase chain reaction (RT-PCR) was used to screen out miRNAs which were expressed with significant differences in the serum of patients with DR. Bioinformatics was employed to predict the miR-195 related to high mobility group box 1 (HMGB1) regulation. Next, miR-195 was down-regulated or up-regulated in umbilical vein endothelial cells through transfection of miR-195 inhibitor and miR-29b mimics respectively.Then we analyzed expression of HMGB1 mRNA and protein by RT-PCR and Western blot. Results MicroRNA array results showed the expression of miR-195 in DR group is decreased by 8.34 times and 11.47 times compared with DM group and the normal group. RT-PCR verification results conforms to the microRNA array results. Compared with the DM group (F=0.034, t=8.057) and the normal group (F=0.370, t=9.522), the expression of miR-195 in DR group were significantly reduced, the differences were statistically significant (P<0.05). RT-PCR showed that the expression of HMGB1 mRNA was significantly decreased in up-regulation group, compared with blank (F=0.023, t=11.287) and negative control group (F=0.365, t=7.471), the difference was statistically significant (P<0.05). The expression of HMGB1 mRNA was significantly increased in down-regulation group, compared with blank (F=0.053, t=10.871) and negative control group (F=0.492, t=6.883), the difference was statistically significant (P<0.05). Western blot showed that the expression of HMGB1 protein was significantly decreased in up-regulation group, compared with blank (F=0.021, t=8.820) and negative control group (F=0.039, t=7.401), the difference was statistically significant (P<0.05); and significantly increased in down-regulation group, compared with blank (F=0.186, t=10.092) and negative control group (F=0.017, t=12.923), the difference was statistically significant (P<0.05). Conclusion MiR-195 can inhibit the expression of HMGB1, reduce the inflammation and angiogenesis, thereby delaying or inhibiting the occurrence and development of DR. Key words: Diabetic retinopathy/psychology; MicroRNAs; High mobility group proteins; Gene transfer techniques

The role of miR-182 in regulating pineal CLOCK expression after hypoxia-ischemia brain injury in neonatal rats

Circadian rhythm disorder is a common neurological deficit caused by neonatal hypoxic-ischemic brain damage (HIBD). However, little is known about its underlying mechanisms. Our previous studies revealed a significant elevation of clock genes at the protein, but not mRNA, levels in the pineal gland after neonatal HIBD. To investigate the mechanisms of post-transcriptional regulation on clock genes, we screened changes of miRNA levels in the pineal gland after neonatal HIBD using high-throughput arrays. Within the miRNAs whose expression was significantly down-regulated, we identified one miRNA (miR182) that targeted the 3′-untranslated region (3′-UTR) of Clock, a key component of clock genes, and played a crucial role in regulating CLOCK expression after oxygen–glucose deprivation in primarily cultured pinealocytes. Our findings therefore provide new insight on studies of therapeutic targets for circadian rhythm disturbance after neonatal HIBD.

Roles of miR-182 in sensory organ development and cancer.

Micro ribonucleic acids (miRNAs) are a cluster of small non-coding RNA molecules predicted to regulate more than 30% of coding messenger (m)RNAs in the human genome and proven to be essential in developmental and pathological processes. The miR-182 gene was first found to be abundantly expressed in sensory organs and regulates the development of the retina and inner ear. Further studies revealed its roles in osteogenesis and T cell differentiation. In addition, the involvement of miR-182 in cancer initiation and progression has recently been uncovered by a growing body of evidence, the majority of which supports its promoting effects in cell proliferation, angiogenesis, and invasion, as well as distant metastasis of various cancer types. Clinical analyses demonstrated the link of miR-182 expression to poor prognosis in cancer patients. Mechanistically, multiple downstream genes including missing-in-metastasis, microphthalm-associated transcription factor, FoxO1, cylindromatiosis, and others, can be targeted by miR-182 and mediate its roles in cancer. miR-182 is also interconnected with prominent cancer-related signaling pathways, such as transforming growth factor beta and nuclear factor kappa beta. Interestingly, it was shown that in vivo targeting of miR-182 prevented liver metastasis of melanoma. miR-182 is emerging as an important regulator of malignancies, which warrants further study to establish the application potential of miR-182 in cancer diagnosis and treatment.

Abstract 15036: Role of miR-195 in Aneurysm Formation

Introduction: Abdominal aortic aneurysm (AAA) is a degenerative disease of the aorta. Apart from the miR-29 family, miR-195 has been implicated in the regulation of the vascular extracellular matrix (ECM). Our aim was to assess the effect of the miR-15 family in aneurysm formation. Methods and Results: Expression of the miR-15 and miR-29 families was assessed in human aortic tissue. In human aneurysmal tissue, miR-195 expression was reduced to the same extent as miR-29b. In plasma, an inverse correlation of miR-195 was observed with the presence of AAA and aortic diameter. To evaluate the effect of miR-195 in ECM deposition, proteomics analysis was performed on the secretome of murine aortic smooth muscle cells (SMCs) following miRNA manipulation. MiR-195 targeted a cadre of ECM proteins, including collagens, proteoglycans, elastin and proteins associated with elastic microfibrils, albeit miR-29b showed a stronger effect. Systemic administration of cholesterol bound antagomiRs revealed better targeting efficacy of miR-195 compared to miR-29b in the uninjured aorta. A significant increase in aortic elastin expression was observed in wildtype animals injected with antagomiR-195. Yet, in apolipoprotein E-deficient mice receiving angiotensin II, inhibition of miR-29b but not miR-195 led to a significant inhibition of aortic aneurysm formation. Conclusions: We provide the first evidence that miR-195 may contribute to the pathogenesis of aneurysmal disease. Levels of miR-195 were reduced in human aneurysmal tissue and in plasma of patients with AAA. Although, miR-195 emerged as a potent regulator of aortic ECM, its inhibition was less effective than miR-29b in preventing aneurysm formation in preclinical models.

Research advances of microRNA-210

Background MicroRNA(miRNA) is an important regulatory factor that can regulate approximately 30％ human protein-coding genes.The level of miRNA will be changed after the tissue under hypoxia,and the most significant change is of microRNA-210 (miR-210).Objective This review discusses the emerging biochemical functions of this miRNA and explores its potential clinical applications.Content Outline the role of miR-210 in mitochondrial respiration,arrest of DNA repair,vascularbiology and angiogenesis.Trend Provide references for the diagnosis and therapy of miR-210-related disorders. Key words: Hypoxia; MicroRNA; MicroRNA-210; Hypoxia-inducible factor

Restoration of miR-7 expression suppresses the growth of Lewis lung cancer cells by modulating epidermal growth factor receptor signaling

microRNAs are an abundant class of short endogenous non-coding RNAs that function as important regulators of multiple target genes and participate in diverse biological roles in carcinogenesis. However, the role of miR-7 in lung cancer remains unclear and requires further elucidation. In the present study, we found a reduction of miR-7 expression in Lewis lung cancer (3LL) cells originating from mice by real-time RT-PCR. Restoration of miR-7 inhibited 3LL cell proliferation, induced cell apoptosis in vitro and reduced tumorigenicity in vivo. We further confirmed that miR-7 downregulated the expression of both epidermal growth factor receptor (EGFR) and murine leukemia viral oncogene homologue-1 (RAF-1) oncogenes by real-time PCR and western blot analysis. Furthermore, inhibition of EGFR showed similar effects to miR-7 enforcement in 3LL cells. Taken together, these findings revealed that miR-7 acts as an antitumor miRNA in 3LL by targeting and suppressing the expression of both EGFR and RAF-1 oncogenes. This study may provide a rationale for the use of miR-7 in lung cancer target therapy.

Role of miR-195 in aortic aneurysmal disease.

Abdominal aortic aneurysms constitute a degenerative process in the aortic wall. Both the miR-29 and miR-15 families have been implicated in regulating the vascular extracellular matrix. Our aim was to assess the effect of the miR-15 family on aortic aneurysm development. Among the miR-15 family members, miR-195 was differentially expressed in aortas of apolipoprotein E-deficient mice on angiotensin II infusion. Proteomics analysis of the secretome of murine aortic smooth muscle cells, after miR-195 manipulation, revealed that miR-195 targets a cadre of extracellular matrix proteins, including collagens, proteoglycans, elastin, and proteins associated with elastic microfibrils, albeit miR-29b showed a stronger effect, particularly in regulating collagens. Systemic and local administration of cholesterol-conjugated antagomiRs revealed better inhibition of miR-195 compared with miR-29b in the uninjured aorta. However, in apolipoprotein E-deficient mice receiving angiotensin II, silencing of miR-29b, but not miR-195, led to an attenuation of aortic dilation. Higher aortic elastin expression was accompanied by an increase of matrix metalloproteinases 2 and 9 in mice treated with antagomiR-195. In human plasma, an inverse correlation of miR-195 was observed with the presence of abdominal aortic aneurysms and aortic diameter. We provide the first evidence that miR-195 may contribute to the pathogenesis of aortic aneurysmal disease. Although inhibition of miR-29b proved more effective in preventing aneurysm formation in a preclinical model, miR-195 represents a potent regulator of the aortic extracellular matrix. Notably, plasma levels of miR-195 were reduced in patients with abdominal aortic aneurysms suggesting that microRNAs might serve as a noninvasive biomarker of abdominal aortic aneurysms.

MiR-210 over-expression enhances mesenchymal stem cell survival in an oxidative stress environment through antioxidation and c-Met pathway activation.

microRNA-210 (miR-210) has generally been reported to be associated with cell survival under hypoxia. However, there are few data regarding the role of miR-210 in the survival of mesenchymal stem cells (MSCs) under oxidative stress conditions. Thus, we sought to investigate whether miR-210 over-expression could protect MSCs against oxidative stress injury and what the primary mechanisms involved are. The results showed that over-expression of miR-210 significantly reduced the apoptosis of MSCs under oxidative stress, accompanied by obvious increases in cell viability and superoxide dismutase activity and remarkable decreases in malonaldehyde content and reactive oxygen species production, resulting in a noticeable reduction of apoptotic indices when compared with the control. Moreover, the above beneficial effects of miR-210 could be significantly reduced by c-Met pathway repression. Collectively, these results showed that miR-210 over-expression improved MSC survival under oxidative stress through antioxidation and c-Met pathway activation, indicating the potential development of a novel approach to enhance the efficacy of MSC-based therapy for injured myocardium.

Intergenerational effects of a maternal high fat diet on feto-placental development in a rabbit model

Intergenerational effects of a maternal high fat diet on feto-placental development in a rabbit model

Senescent stroma promotes prostate cancer progression: The role of miR-210

We focused our interest on senescent human-derived fibroblasts in the progression of prostate cancer. Hypoxic senescent fibroblasts promote prostate cancer aggressiveness by inducing epithelial to mesenchymal transition (EMT) and by secreting energy-rich compounds to support cancer cell growth. Hypoxic senescent fibroblasts additionally increase: i) the recruitment of monocytes and their M2-macrophage polarization, ii) the recruitment of bone marrow-derived endothelial precursor cells, facilitating their vasculogenic ability and iii) capillary morphogenesis, proliferation and invasion of human mature endothelial cells. In addition, we highlight that overexpression of the hypoxia-induced miR-210 in young fibroblasts increases their senescence-associated features and converts them into cancer associated fibroblast (CAF)-like cells, able to promote cancer cells EMT, to support angiogenesis and to recruit endothelial precursor cells and monocytes/macrophages.

Abstract 496: Extracellular Matrix Secretion by Vascular Smooth Muscle Cells: Role of MiR-195 and MiR-29b

Rationale: Extracellular matrix (ECM) remodeling is a key function of vascular smooth muscle cells (SMCs). MicroRNAs (miRNAs), in particular the miR-29 family and miR-195, have been implicated in the control of ECM secretion. Objective: To perform a proteomics comparison of miRNA effects on ECM production by vascular SMCs. Methods and Results: Murine SMCs were transfected with miRNA mimics and antimiRs of miR-29b and miR-195, and their conditioned medium was analyzed by mass spectrometry. Both miRNAs targeted a cadre of ECM proteins, including proteoglycans, collagens, proteases, elastin and proteins associated with elastic microfibrils, albeit miR-29 showed a stronger effect. The proteomics findings were subsequently validated at the transcription level using quantitative polymerase chain reaction. Similar to miR-29, in vivo inhibition of miR-195 by intraperitoneal injection of cholesterol bound antagomiRs led to significant alterations of elastin expression in murine aortas. Since elastin degradation is a key event in aortic aneurysm formation, we investigated miR-195 expression in patients. In human aortic aneurysmal tissue, miR-195 expression was reduced compared to non-aneurysmal tissue. In plasma, a comparison between male patients with abdominal aortic aneurysms and controls matched for diabetes and hypertension returned a panel of five highly correlated miRNAs: miR-195, miR-125b, miR-148a, miR-20a and miR-340 showed significant inverse associations with the presence of abdominal aortic aneurysms and aortic diameter, with miR-195 dominating in terms of association strength. Conclusions: Using proteomic analysis, we compared the effect of miR-29 and miR-195 on ECM secretion by vascular SMCs and identified novel miRNA targets. Findings in patients support an important role for miR-195 in vascular remodeling as evidenced by reduced miR-195 expression in human aneurysmal tissue and an inverse correlation between plasma miR-195 levels and aortic diameter.