Expression Of miRNA-16 Research Articles

Sensitivity of miRNA-181a, miRNA-23b and miRNA-16 in the Late-Onset Neonatal Sepsis: A Diagnostic Study

Abstract Objective To evaluate the expression and diagnostic value of levels of the microRNAs (miRNAs), miRNA-181a, miRNA-23b, and miRNA-16, in late-onset neonatal sepsis (LOS) and compare them with the diagnostic utility of C-reactive protein (CRP) levels. Methods This was a prospective diagnostic study conducted between January 2021 and March 2023 at a tertiary care center (Sri Ramachandra Hospital) in India. Quantitative real-time polymerase chain reaction was performed to determine miRNA-181a, miRNA-23b, and miRNA-16 expression levels, and CRP was measured by nephelometry. The diagnostic value of miRNA and CRP levels were analyzed using receiver operating characteristic (ROC) curves. ROC curves were utilized to determine optimal cutoff points, and Mann–Whitney tests were performed using SPSS to ascertain P values, with statistical significance defined as <0.05. Results This study included 100 samples, with 50 cases of culture-proven LOS (27 females, 23 males) and 50 healthy controls (31 females, 19 males). In LOS, miRNA-181a and miRNA-23b expression levels were significantly downregulated (P < 0.001), with area under the curve (AUC) values of 0.83 and 0.92, respectively, whereas those of miRNA-16 were significantly upregulated (P < 0.001; AUC = 0.97). In comparison, CRP levels had an AUC value of 0.831 (P < 0.001). Further, miRNA-23b showed the highest sensitivity (98%) of markers tested, whereas miRNA-16 exhibited the highest specificity (96%). Conclusion MiRNA, especially miRNA-16, shows diagnostic potential for neonatal sepsis compared with traditional biomarkers like CRP and procalcitonin, suggesting its use as an early marker for LOS. However, further cohort studies are needed before practical application.

Statement of Retraction: Two Cu(II) complexes: inhibitory activity on ovarian cancer cell proliferation, migration, and invasion ability via increasing miRNA16 expression

Statement of Retraction: Two Cu(II) complexes: inhibitory activity on ovarian cancer cell proliferation, migration, and invasion ability via increasing miRNA16 expression

Diagnostic and prognostic significance of miRNA-511 and miRNA-16 expressions in adult patients with B-acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia (ALL) is a neoplastic disease that results from multistep somatic mutations in a single lymphoid progenitor cell. MicroRNAs (miRNAs) are critical regulators of gene expression, tumor suppression, and oncogenesis. Aim To evaluate miRNA-511 and miRNA-16 expression in Egyptian adult patients with B-ALL. Patients and methods A total of 37 newly diagnosed adult patients with B-ALL admitted to Alexandria Main University Hospital in 2019 were included. Complete blood count, bone marrow aspiration, immunophenotyping, BCR-ABL testing, karyotyping, miRNA extraction using miRNeasy Mini followed by cDNA synthesis AQ6 (RQ-PCR combines cDNA synthesis from RNA templates using miScript II RT kit), and finally real-time PCR for miRNA-511 and miRNA-16 expression were among the investigations that were conducted. Results Mean age of patients with ALL was 30.65 ± 10.39 years, with male to female ratio of 1.4 : 1. Cytogenetic findings showed that only three patients had favorable risk, and the rest were either intermediate risk (19) or high risk (15). Among the high-risk group, there were 11 patients with Philadelphia chromosome (BCR-ABL 190) positive. Regarding the expression of miRNAs, most patients showed overexpression of both miRNA-16 and miRNA-511. MiRNA-511 was overexpressed in 81.1% (30) patients; among these patients, 43.3% (13) had adverse cytogenetic findings. MiRNA-16 was overexpressed in 70.3% (26) of patients, and half of them (13) had adverse cytogenetic findings. receiver operating characteristic curves showed diagnostic significance in B-ALL for miRNA-16, with sensitivity of 75.7% and specificity of 80%, and for miRNA-511, sensitivity was 89.2% and specificity was 90% (P<0.05). Conclusion MiRNA-16 and miRNA-511 were significantly overexpressed in adult patients with B-ALL. They have a role in diagnosis but a weak role in patient prognosis.

RETRACTED ARTICLE: Two Cu(II)-based coordination polymers: inhibitory activity on the ovarian cancer cell invasion and migration by regulating the miRNA16 expression

We, the Editors and Publisher of the journal Inorganic and Nano-Metal Chemistry, have retracted the following article: Dong-Mei Yang, Li-Hong Huang, Qiong Xia, Ai-Ling Li & Yu Chen (2022): Two Cu (II)-based coordination polymers: inhibitory activity on the ovarian cancer cell invasion and migration by regulating the miRNA16 expression, Inorganic and Nano-Metal Chemistry, DOI: 10.1080/24701556.2022.2034009 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors do not agree with the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

ALL-443: Diagnostic and Prognostic Significance of miRNA-511 and miRNA-16 Expression in Adult B-Acute Lymphoblastic Leukemia Patients

Acute lymphoblastic leukemia (ALL) is a neoplastic disease that results from multistep somatic mutations in a single lymphoid progenitor cell. MicroRNAs (miRNAs) are critical regulators of gene expression, tumor suppression, and oncogenesis. <h3>Aim:</h3> To evaluate miRNA-511 and miRNA-16 expression in Egyptian adult B-ALL. <h3>Subjects and Methods:</h3> 37 newly diagnosed adult B-ALL patients admitted to Alexandria Main University Hospital in 2019. Investigations included CBC, bone marrow aspiration, immunophenotyping, BCR-ABL testing, karyotyping, miRNA extraction using miRNeasy Mini Kit, qRT-PCR combined with cDNA synthesis from RNA templates using miScript II RT Kit, followed by real-time PCR for miR-511 and miR-16 expression analysis. <h3>Results:</h3> Mean age of ALL patients was 30.65 ± 10.39 years, with a male to female ratio of 1.4:1. Cytogenetic findings showed only 3 patients had favorable risk, and the rest were either intermediate risk (19) or high risk (15). Among the high-risk group, 11 patients were Philadelphia (BCR-ABL 190)-positive. Regarding the expression of the miRNAs, most patients showed the overexpression of both miR-16 and miR-511. MiR-511 was overexpressed in 81.1% (30) of patients; among these patients, 43.3% (13) had adverse cytogenetic findings. MiR-16 was overexpressed in 70.3% (26) of patients; half of them (13) had adverse cytogenetic findings. ROC curves showed the diagnostic significance in B-ALL of miR-16, with a sensitivity of 75.7% and a specificity of 80%; for miR-511, the sensitivity was 89.2%, and specificity was 90%, (p<0.05). Among the studied group, 9 (24%) patients developed COVID-19 viral infection, and of those, 3 (33%) patients died, comprising 21% of all deaths. The three patients were either refractory or relapsed and treated mostly as palliative cases. <h3>Conclusion:</h3> MiR-16 and miR-511 were significantly overexpressed in adult B-ALL. They have a role in diagnosis but a weak role in patients' prognosis.

AB0114 INVESTIGATION OF THE EFFECTS OF EXERCISE ON MIRNA EXPRESSIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background:The goal of treatment for patients with RA is achieve to remission, or at least a state of low disease activity. Exercise is recommended for patients with RA in addition to drug therapy. It has been found to be effective in greatly improving functionality and reducing cardiovascular risk without exacerbating disease activity. Therefore, it is recommended that all RA patients should be encouraged to include aerobic and resistant exercise training as part of their routine treatment (1).miRNAs(miRNA) are known to protect the pathophysiological process specific to RA. miRNA-146a is one of the miRNAs extensively studied in RA, its expression was found to be higher in the synovial fluid and synovial tissue of RA patients compared to healthy individuals (2).Many studies have found that miRNA-146a, along with miRNA-16 and miRNA155 may be related to disease pathology. It has also been found that high levels of miRNA-16 expression correlate with active disease and low levels of expression with inactive disease. It has been found that the increased level of miRNA-155 causes a problem in the modulation of arthritis It has been found that the expression level of miRNA-145 is increased in peripheral blood mononuclear cells of RA patients and synovium supporting osteoclastogenesis (3,4,5).Objectives:It is aimed to investigate the effect of exercise on microRNA expressions in patients with rheumatoid arthritis (RA).Methods:30 patients and 30 healthy controls aged 18-60 years who met the 2010 ACR / EULAR RA criteria were included in the study. A program consisting of strengthening and stretching exercises 2 days a week was applied to the study group for 8 weeks. One day a week, 30 minutes of mild moderate walking was requested. Of the cases at the beginning and at the end of the treatment; 5-10 cc peripheral blood samples were taken into one EDTA tube. Then Numeric Rating Scale (NRS) was used for pain, 28-joint Disease Activity Score (DAS28) was used to calculate disease activity, Health Assessment Questionnaire (HAQ) was used to assess general health and Short Form-36 (SF-36) was used to evaluate quality of life. 5-10 cc peripheral blood samples were taken to only 1 EDTA tube of the control group. In the samples taken, gene expressions of miRNA-146a, miRNA-155, miRNA-16, miRNA-145 were determined by real-time PZR method.Results:There was a significant difference in DAS28, SF-36, NRS, HAQ scales before and after treatment in the RA group of patients (p 0.05). The expression level of MiRNA-146a does not differ significantly before and after treatment (p&gt; 0.05). However, these two groups differ significantly with the control group (p 0.05). No significant difference was observed in the miRNA-155 and miRNA-16 expression levels in the pretreatment, posttreatment, and control groups (p&gt; 0.05).Conclusion:Exercise therapy has a good effect on pain, disease activity, quality of life and general health in patients with RA. It has been found that exercise can affect vii some of the miRNAs involved in disease pathogenesis. However, more comprehensive studies are needed.

A Zn(ii)–organic cage with semirigid ligand for solvent-free cyanosilylation and inhibitory effect on ovarian cancer cell migration and invasion ability via regulating mi-RNA16 expression

Abstract[Zn6(L)4(DMF)2(H2O)4](1,4-Dioxane)2(DMF)10(H2O)4 (1, L = 4,4′,4″-(benzene-1,3,5-triyltris(oxy))tribenzoate), the metal-organic cage, was produced via Zn(NO3)2·6H2O reacting with the H3L ligand in the mixed solvent of DMF and water. The heterogeneous catalytic activities of the complex 1 for the aldehydes cyanidation under the conditions of free solvent were studied, which indicates that the removal of coordination solvents could greatly improve the catalytic activities. Furthermore, the inhibitory effect of the compound against the ovarian cancer cells was assessed. The mi-RNA16 relative expression level was measured after exposure to the compound with real-time reverse transcription-polymerase chain reaction. The invasion and migration of cells after compound treatment were also detected by the transwell method.

RETRACTED ARTICLE: Two Cu(II) complexes: inhibitory activity on ovarian cancer cell proliferation, migration, and invasion ability via increasing miRNA16 expression

We, the Editors and Publisher of the journal Inorganic and Nano-Metal Chemistry, have retracted the following article: Yajuan Gu, Chao Deng, Haogang Sun & Daqian Zhang. Two Cu(II) complexes: inhibitory activity on ovarian cancer cell proliferation, migration, and invasion ability via increasing miRNA16 expression, Inorganic and Nano-Metal Chemistry. 2021, volume 51: issue number 2, 246-252, DOI: 10.1080/24701556.2020.1783315 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors have agreed to retract the article. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

LncRNA MORT Inhibits Cancer Cell Proliferation and Promotes Apoptosis in Mantle Cell Lymphoma by Upregulating miRNA-16.

IntroductionLncRNA mortal obligate RNA transcript (MORT) is downregulated in different types of cancer, indicating its involvement in cancer biology.MethodsIn this study, MORT and miRNA-16 were both downregulated in plasma of mantle cell lymphoma (MCL) patients than that in the controls. The low levels of MORT and miRNA-16 were correlated with poor survival of MCL patients. The expression of MORT and miRNA-16 was positively correlated only in MCL patients.ResultsOverexpression of MORT and miRNA-16 suppressed cell proliferation but promoted cancer cell apoptosis, while miRNA-16 inhibitor reduced the effects of MORT overexpression. Overexpression of MORT led to upregulated expression of miRNA-16, while overexpression of miRNA-16 had no effect on the expression of MORT.ConclusionTherefore, MORT may inhibit cancer cell proliferation and promote apoptosis in mantle cell lymphoma by upregulating miRNA-16.

Effect of Electroacupuncture on Reuptake of Serotonin via miRNA-16 Expression in a Rat Model of Depression.

The current study aimed to investigate the effects and mechanisms of electroacupuncture (EA) treatment applied to Bai hui (GV20) and Yin tang (GV29) acupoints (1 mA, 2 Hz, continuous wave, 20 minutes) for 28 days in a rat model of chronic unpredictable mild stress (CUMS) on reuptake of serotonin (5-hydroxytryptamine (5-HT)) and miRNA-16 levels in the hippocampus and serum. Rats were housed in individual cages, and CUMS was used to establish a rat model of depression. After EA treatment for 4 weeks, behavioral changes and indices including 5-HT transporter (SERT), 5-HT, and miRNA-16 levels in the hippocampus and serum were examined. The EA treatment significantly improved base levels of sucrose preference and exploratory behavior and significantly decreased SERT protein and mRNA expression in the hippocampus of depressed rats. Significantly increased 5-HT levels were observed, and miRNA-16 levels were significantly decreased in the hippocampus and serum of depressed rats. In conclusion, the antidepressant effects of EA treatment may be affected via inhibition of 5-HT reuptake, upregulation of 5-HT levels, and inhibition of miRNA-16 expression in the hippocampus and serum.

MiRNA detection in cervical exfoliated cells for missed high-grade lesions in women with LSIL/CIN1 diagnosis after colposcopy-guided biopsy

BackgroundLow-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by colposcopy guided biopsy is recommended conservative follow-up, although some of these lesions are actually high-grade lesions, which are missed on an initial colposcopy. Therefore, in this work, we evaluate the potential role of miRNA detection in cervical exfoliated cells in a clinic-based population for predicting missed high-grade lesions in women diagnosed with LSIL/CIN1 after colposcopy-guided biopsy.MethodsA total number of 177 women with a diagnosis of LSIL/CIN1 obtained by colposcopy-guided biopsy were grouped into two categories according to the histology of the conization specimens: consistent LSIL/CIN1 group (surgical pathology consistent with colposcopic diagnosis) and missed high-grade lesion group (surgical pathology found high-grade lesion). The expression of eight miRNAs, such as miRNA195, miRNA424, miRNA375, miRNA218, miRNA34a, miRNA29a, miRNA16–2, and miRNA20a was detected by real time-quantitative polymerase chain reaction (RT-qPCR) in cervical exfoliated cells of the 177 patients. Pearson Chi-Square was used to compare the performance efficiency of patients’ characteristics. Nonparametric Man-Whitney U test was used to assess differences in miRNA expression. The receiver operating characteristic (ROC) curve was used to assess the performance of miRNA evaluation in detecting missed high-grade lesions.ResultsAmong the 177 women with biopsy-confirmed CIN1, 15.3% (27/177) had CIN2+ in the conization specimen (missed high-grade lesion group) and 84.7% (150/177) had CIN1-(consistent LSIL/CIN1 group). The relative expression of miRNA-195 and miRNA-29a in the missed high-grade lesion group was significantly lower than that in the consistent LSIL/CIN1 group. The relative expression of miRNA16–2 and miRNA20a in the missed high-grade lesion group was significantly higher than that in the consistent LSIL/CIN1 group. No significant difference was observed between these two groups regarding the other four miRNAs. Of these significant miRNAs, miRNA29a detection achieved the highest Youden index (0.733), sensitivity (92.6%), positive predictive value (46.2%), negative predictive value (98.3%) and higher specificity (80.7%) when identifying missed high-grade lesions.ConclusionsDetection of miRNA might provide a new triage for identifying a group at higher risk of missed high-grade lesions in women with colposcopy diagnosis of LSIL/CIN1.

The Crosstalk between Interferon and Transforming Growth Factor Beta Signaling Pathways in Hepatitis C Patients

Background: there is an increasing interest in using microRNAs (miRNAs) as biomarkers in liver disease. Diagnostic biomarkers in hepatitis C serve as a great benefit for the early treatment of HCV. Aim of the Work: the aim of this study was to evaluate the expression of miRNA-16 in Egyptian patients infected with HCV and their relation to different biochemical and clinicopathological parameters. Patients and Methods: twenty-five subjects were chosen, 16 HCV infected and 9 healthy controls. Collection, processing and storage of serum for evaluation of miRNA16 using RT-qPCR was done. We evaluated the power of miRNA as a diagnostic tool using ROC curve analysis. The prognostic significance of the investigated parameters in HCV patients was explored. Results: there is a highly significant difference of miRNA 16 expression between HCV patients and healthy controls. miRNA 16 has great sensitivity and specificity for differentiating between patients with HCV and healthy controls. Conclusion: miRNA 16 can be used as a potential diagnostic biomarker for HCV. In addition, it could be used for staging of the disease.

Exercise Training Restores the Cardiac Microrna-16 Levels Preventing Microvascular Rarefaction in Obese Zucker Rats

Objective: To evaluate the effects of aerobic exercise training (AET) on cardiac miRNA-16 levels and its target gene VEGF related to microvascular rarefaction in obese Zucker rats (OZR). Methods: OZR (n = 11) and lean (L; n = 10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT). Swimming exercise training lasted 60 min, 1×/day/10 weeks, with 4% body weight workload. Cardiac angiogenesis was assessed by histological analysis (periodic acid-Schiff) by calculating the capillary/fiber ratio. The protein expressions of VEGF, VEGFR2, and CD31 were evaluated by western blot. The expression of miRNA-16 was evaluated by real-time PCR. Results: Heart rate decreased in the trained groups compared to sedentary groups. The cardiac capillary/fiber ratio was reduced in OZR compared to L, LT and OZRT groups, indicating that aerobic exercise training (AET) was capable of reversing the microvascular rarefaction in the obese animals. miRNA-16 expression was increased in OZR compared to L, LT and OZRT. In contrast, its target, VEGF protein expression was 24% lower in OZR compared to L group, which has been normalized in OZRT group. VEGFR2 protein expression was increased in trained groups compared to their controls. CD31, a endothelial cells marker, showed increased expression in OZRT compared to OZR, indicating greater vascularization in OZRT group. Conclusion: AET induced cardiac angiogenesis in obese animals. This revascularization is associated with a decrease in miRNA-16 expression permissive for increased VEGF protein expression, suggesting a mechanism for potential therapeutic application in vascular diseases.

Early adolescent stress-induced changes in prefrontal cortex miRNA-135a and hippocampal miRNA-16 in male rats.

Early-life stress increases susceptibility to post-traumatic stress disorders (PTSD), in which the dysfunction of 5-hydroxytryptamine plays an important role. miRNA-135a in the prefrontal cortex (PFC) and miRNA-16 in the hippocampus (HIP) are closely related to the 5-HT neurotransmitter system. Here, we investigated behavior, miRNA-135a in the PFC, miRNA-16 in the HIP, and 5-HT1AR expression in both brain regions in adolescent and adult rats that were exposed to inescapable stress during their adolescence. Paroxetine hydrochloride and corticotropin-releasing factor antagonist (CP-154,526) were used as intervening measures. Our study demonstrated that early adolescent stress induced anxiety-like behaviors and spatial memory damage, a reduction in miRNA-135a expression was associated with increased 5-HT1AR expression in PFC, and increased miRNA-16 expression in the HIP of stressed rats. Drug treatments alleviated behaviors and reversed the miRNA-135a, miRNA-16, and 5-HT1AR expression in stressed rats.

Effects of miRNA-15 and miRNA-16 expression replacement in chronic lymphocytic leukemia: implication for therapy.

Chronic lymphocytic leukemia (CLL) clones are characterized by loss of a critical region in 13q14.3, (del(13)(q14)) involving the microRNA (miRNA) cluster miR-15a and miR-16-1. We have investigated the effects of replacement of miR-15a and miR-16-1. CLL cells transfected with these miRNA mimics exhibited a decrease in cell viability in vitro and impaired capacity for engraftment and growth in NOD/Shi-scid,γcnull (NSG) mice. No synergistic effects were observed when the two miRNA mimics were combined. The phenomena were not restricted to CLL with the del(13)(q14) lesion. Similar effects induced by miRNA mimics were seen in cells with additional chromosomal abnormalities with the exception of certain CLL clones harboring TP53 alterations. Administration of miRNA mimics to NSG mice previously engrafted with CLL clones resulted in substantial tumor regression. CLL cell transfection with miR-15a and miR-16-1-specific inhibitors resulted in increased cell viability in vitro and in an enhanced capacity of the engrafted cells to grow in NSG mice generating larger splenic nodules. These data demonstrate that the strong control by miR-15a and miR-16-1 on CLL clonal expansion is exerted also at the level of full-blown leukemia and provide indications for a miRNA-based therapeutic strategy.

MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study.

Background The identification of diagnostic/prognostic biomarkers for asbestos-related diseases is relevant for early diagnosis and patient survival and may contribute to understanding the molecular mechanisms underlying the disease development and progression. Aims To identify a pattern of miRNAs as possible diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and asbestosis (ASB) and as prognostic biomarkers for MPM patients. Methods miRNA-16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin-fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles compared to patients with other noncancerous pulmonary diseases (controls). Results. The expression of all the miRNAs was significantly lower in patients with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in plasma and tissue of MPM patients were significantly correlated. Furthermore, the expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was positively related with cumulative survival in MPM patients. Conclusions All the miRNA levels were decreased in patients with MPM or ASB, supporting the role of circulating miRNAs as a potential tool for diseases associated with exposure to asbestos fibers. miRNA-16 was directly related to MPM patient prognosis, suggesting its possible use as a prognostic marker in MPM patients.

Noninvasive Visualization of MicroRNA-16 in the Chemoresistance of Gastric Cancer Using a Dual Reporter Gene Imaging System

MicroRNAs (miRNAs) have been implicated to play a central role in the development of drug resistance in a variety of malignancies. However, many studies were conducted at the in vitro level and could not provide the in vivo information on the functions of miRNAs in the anticancer drug resistance. Here, we introduced a dual reporter gene imaging system for noninvasively monitoring the kinetic expression of miRNA-16 during chemoresistance in gastric cancer both in vitro and in vivo. Human sodium iodide symporter (hNIS) and firefly luciferase (Fluc) genes were linked to form hNIS/Fluc double fusion reporter gene and then generate human gastric cancer cell line NF-3xmir16 and its multidrug resistance cell line NF-3xmir16/VCR. Radioiodide uptake and Fluc luminescence signals in vitro correlated well with viable cell numbers. The luciferase activities and radioiodide uptake in NF-3xmir16 cells were remarkably repressed by exogenous or endogenous miRNA-16. The NF-3xmir16/VCR cells showed a significant increase of 131I uptake and luminescence intensity compared to NF-3xmir16 cells. The radioactivity from in vivo 99mTc-pertechnetate imaging and the intensity from bioluminescence imaging were also increased in NF-3xmir16/VCR compared with that in NF-3xmir16 tumor xenografts. Furthermore, using this reporter gene system, we found that etoposide (VP-16) and 5-fluorouracil (5-FU) activated miRNA-16 expression in vitro and in vivo, and the upregulation of miRNA-16 is p38MAPK dependent but NF-κB independent. This dual imaging reporter gene may be served as a novel tool for in vivo imaging of microRNAs in the chemoresistance of cancers, as well as for early detection and diagnosis in clinic.

The Induction of microRNA-16 in Colon Cancer Cells by Protein Arginine Deiminase Inhibition Causes a p53-Dependent Cell Cycle Arrest

Protein Arginine Deiminases (PADs) catalyze the post-translational conversion of peptidyl-Arginine to peptidyl-Citrulline in a calcium-dependent, irreversible reaction. Evidence is emerging that PADs play a role in carcinogenesis. To determine the cancer-associated functional implications of PADs, we designed a small molecule PAD inhibitor (called Chor-amidine or Cl-amidine), and tested the impact of this drug on the cell cycle. Data derived from experiments in colon cancer cells indicate that Cl-amidine causes a G1 arrest, and that this was p53-dependent. In a separate set of experiments, we found that Cl-amidine caused a significant increase in microRNA-16 (miRNA-16), and that this increase was also p53-dependent. Because miRNA-16 is a putative tumor suppressor miRNA, and others have found that miRNA-16 suppresses proliferation, we hypothesized that the p53-dependent G1 arrest associated with PAD inhibition was, in turn, dependent on miRNA-16 expression. Results are consistent with this hypothesis. As well, we found the G1 arrest is at least in part due to the ability of Cl-amidine-mediated expression of miRNA-16 to suppress its' G1-associated targets: cyclins D1, D2, D3, E1, and cdk6. Our study sheds light into the mechanisms by which PAD inhibition can protect against or treat colon cancer.

Overexpression of microRNA-16-2 contributes to the abnormal erythropoiesis in polycythemia vera

AbstractDeregulated expression of microRNAs is associated with neoplasia. Here, we show that mature miR-16 levels are abnormally increased in CD34+ cells of patients with polycythemia vera as a consequence of preferential expression of miR-16-2 on chromosome 3 rather than of miR-16-1 on chromosome 13. Forced expression of miRNA-16 in normal CD34+ cells stimulated erythroid cell proliferation and maturation. Conversely, exposure of polycythemia vera CD34+ cells to small interfering RNA against pre-miR-16-2 reduced erythroid colonies and largely prevented formation of erythropoietin-independent colonies; myeloid progenitors remained unaffected. Experiments with knock down of JAK2 indicated that overexpression of miR-16 was independent of JAK/STAT pathway activation. Mice injected with an miR-16 antagomir showed a blunted erythroid response to exogenous erythropoietin, which indicates a role of miR-16 in normal erythropoiesis. These data suggest that deregulation of miR-16-2 contributes to abnormal expansion of erythroid lineage in polycythemia vera. However, the mechanisms for miR-16-2 overexpression remain to be elucidated, because no genetic abnormalities at the miR-16-2 locus were discovered.