[Retracted] MicroRNA­448 inhibits the progression of retinoblastoma by directly targeting ROCK1 and regulating PI3K/AKT signalling pathway.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that three data panels featured in the flow cytometric plots shown in Figs. 5D and 6D, and several panels from the cell invasion assays shown in Figs. 5C and 6C, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 2402­2412, 2018; DOI: 10.3892/or.2018.6302].

LncRNA XIST sponges microRNA-448 to promote malignant behaviors of colorectal cancer cells via regulating GRHL2.

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are essential regulators in human cancers, while the role of lncRNA X-inactive-specific transcript (XIST) in colorectal cancer (CRC) via regulating miR-448 remains largely unknown. Herein, we aimed to elucidate the effect of the XIST/miR-448/grainyhead-like 2 (GRHL2) axis on CRC development. XIST, miR-448, and GRHL2 expression in CRC tissues from patients and in human CRC cell lines was assessed. Loss- and gain-function assays were implemented to unveil the roles of XIST, miR-448, and GRHL2 in screened CRC cells. The tumor growth in vivo was observed in nude mice. Binding relations among XIST, miR-448, and GRHL2 were evaluated. XIST and GRHL2 expressed highly whereas miR-448 expressed lowly in CRC tissues and cells. XIST or GRHL2 downregulation, or miR-448 elevation suppressed the malignant behaviors of CRC cells in vitro, and downregulated XIST or upregulated miR-448 also inhibited the tumor growth in vivo. miR-448 upregulation reversed the role of XIST elevation in CRC cells. XIST particularly bound to miR-448, and miR-448 targeted GRHL2. Knockdown of XIST upregulates miR-448 to impede malignant behaviors of CRC cells via inhibiting GRHL2. This study may provide novel biomarkers for CRC diagnosis and treatment.

Inhibition of microRNA-448 suppresses CD4+ T cell inflammatory activation via up-regulating suppressor of cytokine signaling 5 in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. MicroRNA-448 (miR-448) has a pro-inflammatory effect in various inflammation-related diseases and is up-regulated in serum of patients with SLE. However, the role of miR-448 in SLE development remains elusive. In our study, we found high expression of miR-448 in peripheral blood mononuclear cells (PBMCs) of SLE patients, and miR-448 level was positively associated with disease severity. Besides, miR-448 level was up-regulated during the growth of MRL/lpr mice. To investigate the function of miR-448 in SLE, we subjected 8-week MRL/lpr mice to injection of lentivirus (LV)-mediated anti-miR-448. Inhibition of miR-448 reduced serum IgG and anti-dsDNA IgG contents, 24 h urine protein and blood urea nitrogen (BUN) levels, increased complement C3 concentration, and ameliorated splenomegaly and lymphadenectasis in MRL/lpr mice. MiR-448 inhibition alleviated renal inflammatory infiltration and glycogen deposition. Moreover, miR-448 inhibition promoted Treg cell activation and inhibited Th17 cell proportion in naïve CD4+ T cells from spleens, along with elevated interleukin (IL)-10 and reduced IL-17A levels. In vitro, miR-448 inhibition diminished CD4+ T cell polarization toward Th17 cells under Th17-polarizing conditions. Further, luciferase reporter assay revealed that miR-448 binds to the 3'UTR of suppressor of cytokine signaling 5 (SOCS5). SOCS5 expression was down-regulated in the spleens of MRL/lpr mice and induced Th17 cells. SOCS5 deficiency partially reversed the role of miR-448 in Th17 differentiation and IL-17A expression in SLE. Taken together, inhibition of miR-448 impedes Th17 cell activation and tissue damages via targeting SOCS5 in SLE.

Long non­coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation­induced pyroptosis via microRNA­448/gasdermin E in colorectal cancer cells.

Pyroptosis is mediated by gasdermins and serves a critical role in ionizing radiation (IR)­induced damage in normal tissues, but its role in cancer radiotherapy and underlying mechanisms remains unclear. Long non­coding (lnc) RNAs serve important roles in regulating the radiosensitivity of cancer cells. The present study aimed to investigate the mechanistic involvement of lncRNAs in IR­induced pyroptosis in human colorectal cancer HCT116 cells. LncRNA, microRNA (miR)­448 and gasdermin E (GSDME) levels were evaluated using reverse transcription­quantitative polymerase chain reaction. Protein expression and activation of gasdermins were measured using western blotting. The binding association between miR­448 and GSDME was assessed using the dual­luciferase reporter assay. Pyroptosis was examined using phase­contrast microscopy, flow cytometry, Cell Counting Kit­8 assay and lactate dehydrogenase release assay. IR dose­dependently induced GSDME­mediated pyroptosis in HCT116 cells. GSDME was identified as a downstream target of miR­448. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was upregulated in response to IR and enhanced GSDME expression by negatively regulating miR­448 expression. Notably, NEAT1 knockdown suppressed IR­induced pyroptosis, full­length GSDME expression and GSDME cleavage compared with that in irradiated cells. In addition, NEAT1 knockdown rescued the IR­induced decrease in cell viability in HCT116 cells. The findings of the present study indicated that lncRNA NEAT1 modulates IR­induced pyroptosis and viability in HCT116 cells via miR­448 by regulating the expression, but not activation of GSDME. The present study provides crucial mechanistic insight into the potential role of lncRNA NEAT1 in IR­induced pyroptosis.

KDM5B promotes self-renewal of hepatocellular carcinoma cells through the microRNA-448-mediated YTHDF3/ITGA6 axis.

Histone methylation plays important roles in mediating the onset and progression of various cancers, and lysine-specific demethylase 5B (KDM5B), as a histone demethylase, is reported to be an oncogene in hepatocellular carcinoma (HCC). However, the mechanism underlying its tumorigenesis remains undefined. Hence, we explored the regulatory role of KDM5B in HCC cells, aiming to identify novel therapeutic targets for HCC. Gene Expression Omnibus database and StarBase were used to predict important regulatory pathways related to HCC. Then, the expression of KDM5B and microRNA-448 (miR-448) in HCC tissues was detected by RT-qPCR and Western blot analysis. The correlation between KDM5B and miR-448 expression was analysed by Pearson's correlation coefficient and ChIP experiments, and the targeting of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) by miR-448 was examined by luciferase assay. Additionally, the effect of KDM5B on the proliferation, migration, invasion and apoptosis as well as tumorigenicity of transfected cells was assessed using ectopic expression and depletion experiments. KDM5B was highly expressed in HCC cells and was inversely related to miR-448 expression. KDM5B demethylated H3K4me3 on the miR-448 promoter and thereby inhibited the expression of miR-448, which in turn targeted YTHDF3 and integrin subunit alpha 6 (ITGA6) to promote the malignant phenotype of HCC. Moreover, KDM5B accelerated HCC progression in nude mice via the miR-448/YTHDF3/ITGA6 axis. Our study uncovered that KDM5B regulates the YTHDF3/ITGA6 axis by inhibiting the expression of miR-448 to promote the occurrence of HCC.

PRDM16 Upregulation Induced by MicroRNA-448 Inhibition Alleviates Atherosclerosis via the TGF-ß Signaling Pathway Inactivation.

The dysregulated expression of microRNAs (miRs) has been associated with pathological and physiological processes of atherosclerosis (AS). In addition, PR domain-containing 16 (PRDM16), a transcriptional mediator of brown fat cell identity and smooth muscle cell activities, may be involved in the hypercholesterolemia during development of AS. The bioinformatic analysis identified a regulatory miR-448 of PRDM16. Hence, the current study aimed to explore whether miR-448 influenced the activities of aortic smooth muscle cell (ASMCs) in AS. We validated that miR-448 was highly expressed in peripheral blood of patients with AS and aortic smooth muscle of AS model mice. Whereas, PRDM16 was downregulated in the aortic smooth muscle of AS model mice. PRDM16 overexpression was observed to inhibit oxidative stress injury and cell proliferation, and promote apoptosis of ASMCs. Mechanistic studies revealed that miR-448 targeted PRDM16 and negatively regulated the PRDM16 expression, while PRDM16 blocked the TGF-ß signaling pathway. Furthermore, Downregulated miR-448 alleviated oxidative stress injury, and attenuated ASMC cell proliferation, migration and enhanced cell apoptosis through upregulation of PRDM16. Taken together, silencing of miR-448 upregulates PRDM16 and inactivates the TGF-ß signaling pathway, thereby impeding development of AS by repressing the proliferation, migration and invasion of ASMCs.

Inhibitory role of long non-coding RNA OIP5-AS1 in rheumatoid arthritis progression through the microRNA-448-paraoxonase 1-toll-like receptor 3-nuclear factor κB axis.

NEW FINDINGS: What is the central question of this study? What are the functions of long non-coding (lnc) RNA OIP5-AS1 in development of rheumatoid arthritis inflammation and what is the molecular mechanism? What is the main finding and its importance? LncRNA OIP5-AS1 mitigates rheumatoid arthritis progression through the competitive endogenous RNA network involving the miR-448-paraoxonase 1 axis and through the inactivation of the toll-like receptor 3-nuclear factor κB signalling pathway. This study may offer new ideas for molecularly based control of rheumatoid arthritis. ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disorder with dysregulation of long non-coding RNAs (lncRNAs) possibly involved. This study aimed to inquire into the roles of lncRNA OIP5-AS1 in RA progression. A rat model of RA was induced. Overexpression of OIP5-AS1 was introduced in the model rats, and the changes in paw swelling, RA severity and the inflammatory factors interleukin (IL)-1ß, IL-10, IL-6 and tumour necrosis factor α were measured. Fibroblast-like synoviocytes (FLSs) from RA patients were collected for in vitro experiments. A gain- and loss-of function study of OIP5-AS1, miR-448 and paraoxonase 1 (PON1) was performed to explore their roles in RA-FLS growth, apoptosis and inflammation. A toll-like receptor 3 (TLR3)-specific agonist, polyinosine-polycytidylic acid, or a nuclear factor κB (NF-κB)-specific antagonist, QNZ, was administrated in RA-FLSs. Consequently, overexpression of OIP5-AS1 reduced the symptom severity and the levels of inflammatory factors in RA rats. OIP5-AS1 could bind to miR-448 to up-regulate PON1 expression. Further overexpression of miR-448 reversed the effects of OIP5-AS1, while overexpression of PON1 inhibited RA-FLS growth and inflammation. In addition, TLR3 activation promoted RA progression. To conclude, this study evidenced that lncRNA OIP5-AS1 may mitigate RA progression through the miR-448-PON1 axis and through the inactivation of the TLR3-NF-κB signalling pathway.

KDM5B-mediated microRNA-448 up-regulation restrains papillary thyroid cancer cell progression and slows down tumor growth via TGIF1 repression.

OBJECTIVE: Papillary thyroid cancer (PTC) is the most ordinary type of thyroid cancer. Studies pivoting on the mechanisms of microRNAs (miRNAs) are adequately explored but not much on miR-448 in PTC. Thus, this study is proposed to bring forward the uncovered mechanisms of miR-448 in PTC. METHODS: Lysine specific demethylase 5B (KDM5B), miR-448 and transforming growth factor ß-induced factor 1 (TGIF1) expression in PTC tissues and cell lines were detected. The connection between miR-448 expression and clinicopathological characteristics of PTC patients was determined. PTC cell lines TPC-1 and K-1 were transfected with sh-KDM5B, si-TGIF1 or miR-448 mimic to explore their roles in PTC cell progression. Tumor xenografts in nude mice was performed to detect tumor volume and weight. RESULTS: KDM5B and TGIF1 were increased and miR-448 was declined in PTC tissues and cell lines. MiR-448 expression was connected with N stage, lymph node metastasis and advanced tumor node metastasis stage of PTC patients. KDM5B knockdown or TGIF1 reduction or miR-448 elevation undermined PTC cell progression and inhibited tumor growth of nude mice. Down-regulation of miR-448 followed by KDM5B knockdown reversed the effect of decreased KDM5B on the proliferation inhibition and apoptosis promotion of PTC cells. CONCLUSION: Our study elaborates that KDM5B-mediated miR-448 up-regulation restrains PTC cell progression and slows down tumor growth via TGIF1 repression, which provides a novel reference for treatment of PTC.

MicroRNA-448 overexpression inhibits fibroblast proliferation and collagen synthesis and promotes cell apoptosis via targeting ABCC3 through the JNK signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a condition that results in the progressive deterioration of lung function with poor prognosis. The current study is aimed at exploring how microRNA-448 (miR-448) targeting ABCC3 affects fibroblast proliferation, apoptosis, and collagen synthesis of mice with IPF via the Jun N-terminal kinase (JNK) signaling pathway. Bioinformatics and dual-luciferase polymerase chain reaction were used to predict the relationship of miR-448 and ABCC3. The expression of miR-448 and ABCC3 was detected in IPF tissues. Using IPF mouse models, lung fibroblasts for the experiments were treated with miR-448 mimic, miR-448 inhibitor, si-ABCC3, or SP600125 (inhibitor of JNK) to evaluate the cell proliferation and apoptosis in response to miR-448. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to identify the expression of miR-448, ABCC3, and the activation of the JNK signaling pathway. ABCC3 was targeted and downregulated by miR-448 based on bioinformatics prediction and dual-luciferase reporter gene assay. Additionally, miR-448 was found to be highly expressed in IPF lung tissues with low expression levels of ABCC3. In response to the treatment of miR-448 mimic or si-ABCC3, lung fibroblasts exhibited decreased cell proliferation and increased apoptotic rates, whereas the miR-448 inhibitor reversed the conditions. Notably, we also found that miR-448 mimic inhibited the JNK signaling pathway. In conclusion, by using miR-448 to target and downregulate ABCC3 to block the JNK signaling pathway in mice with IPF, we found an increase in fibroblast apoptosis, inhibited cell proliferation, and decreased collagen synthesis of fibroblasts.

MicroRNA-448 modulates the progression of neuropathic pain by targeting sirtuin 1.

MicroRNAs (miRNAs) play crucial roles in the pathogenesis of neuropathic pain. The present study investigated the effects of miR-448 on the progression of neuropathic pain in a rat model of chronic constriction injury (CCI) of the sciatic nerve. Reverse-transcription quantitative polymerase chain reaction was conducted to detect the gene expression. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to assess the pain threshold. The protein expression levels of interleukin (IL)-6, IL-1ß and tumor necrosis factor-α (TNF-α) were detected by ELISA. The target of miR-448 was predicted by TargetScan software. The Student's t-test or one-way ANOVA were used to identify statistical differences among groups. miR-448 was persistently upregulated in CCI rats, and both mechanical allodynia and thermal hyperalgesia in CCI rats were decreased following miR-448 downregulation. The expression levels of IL-1ß, IL-6 and TNF-α were significantly increased in CCI rats compared with controls, and these effects were reversed following treatment with a miR-448 inhibitor. A luciferase reporter assay revealed that sirtuin 1 (SIRT1) was a target gene of miR-448. SIRT1 was found to abrogate the effect of miR-448 on neuropathic pain development. Collectively, the results of the present study revealed that miR-448 promoted neuropathic pain in CCI rats by regulating neuroinflammation via SIRT1. Therefore, SIRT1 may be considered as a novel biomarker for neuropathic pain.

miR-448 promotes progression of non-small-cell lung cancer via targeting SIRT1.

Deregulation of microRNAs (miRs) has been demonstrated to be involved in both the initiation and the development of non-small-cell lung cancer (NSCLC). miR-448 has been identified as a tumor suppressor in several cancer types. The aim of the present study was to explore the role of miR-448 in NSCLC. Tumor tissues and paired normal tissues were obtained from patients with NSCLC. The viability and migration of A549 cells were determined by the Cell Counting kit-8 and wound-healing assays, respectively. Gene and protein levels were detected by reverse transcription-quantitative polymerase chain reaction analysis and western blotting, respectively. The interaction between the 3' untranslated region of sirtuin1 (SIRT1) and miR-448 was predicted by TargetScan and verified by dual luciferase reporter assay. miR-448 levels were revealed to be decreased whereas SIRT1 levels were increased in NSCLC tissues compared with normal tissues. Pearson's correlation analysis demonstrated that there was a negative correlation between miR-448 and SIRT1 mRNA levels. Overexpression of miR-448 led to reduced growth and migration ability of A549 cells. In addition, overexpression of miR-448 decreased SIRT1 mRNA and protein levels, thereby inhibiting epithelial-mesenchymal transition (EMT) and affecting EMT-associated molecules, including vimentin and E-cadherin. Dual luciferase reporter assay confirmed that SIRT1 was a direct target of miR-448. Notably, activation of SIRT1 by resveratrol treatment partially reversed the cell growth inhibition induced by miR-448 mimics. These findings suggested that the progression of NSCLC may be controlled by miR-448, which appears to hold promise as a therapeutic target for patients with NSCLC.

microRNA-448 inhibits stemness maintenance and self-renewal of hepatocellular carcinoma stem cells through the MAGEA6-mediated AMPK signaling pathway.

Hepatocellular carcinoma (HCC) occurs mainly in patients with chronic liver disease and cirrhosis. Increasing evidence has identified the involvement of microRNAs (miRNAs) acting as essential regulators in the progression of HCC. As predicted by microarray analysis, miR-448 might potentially affect HCC progression by regulating the melanoma-associated antigen (MAGEA). Therefore, the present investigation focused on exploring whether or not miR-448 and MAGEA6 were involved in the self-renewal and stemness maintenance of HCC stem cells. The interaction among miR-448, MAGEA6, and the AMPK signaling pathway was evaluated. It was noted that miR-448 targeted and downregulated MAGEA6, thus activating the AMP-activated protein kinase (AMPK) signaling pathway in HCC. Furthermore, for the purpose of exploring the functional relevance of MAGEA6 and miR-448 on the sphere formation, colony formation, and invasion and migration of HCC stem cells, the CD133+ CD44 + HCC stem cells were sorted and treated with the mimic or inhibitor of miR-448, small interfering RNA (siRNA) against MAGEA6 or an AMPK activator AICAR. MAGEA6 silencing or miR-448 overexpression was demonstrated to inhibit the abilities of sphere formation, colony formation, cell migration, and invasion of HCC cells. Afterwards, a rescue experiment was conducted and revealed that MAGEA6 silencing reversed the effects of miR-448 inhibitor on stemness maintenance and self-renewal of HCC stem cells. Finally, after the in vivo experiment was carried out, miR-448 was observed to restrain the tumor formation and stemness in vivo. Altogether, miR-448 activates the AMPK signaling pathway by downregulating MAGEA6, thus inhibiting the stemness maintenance and self-renewal of HCC stem cells, which identifies miR-448 as a new therapeutic strategy for HCC.

MiR-448-5p inhibits TGF-ß1-induced epithelial-mesenchymal transition and pulmonary fibrosis by targeting Six1 in asthma.

MicroRNAs (miRNAs) are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation. The aim of this study was to explore how miR-448-5p affects airway remodeling and transforming growth factor-ß1 (TGF-ß1)-stimulated epithelial-mesenchymal transition (EMT) by targeting Sine oculis homeobox homolog 1 (Six1) in asthma. Asthmatic mice models with airway remodeling were induced with ovalbumin solution. MiRNA expression was evaluated using quantitative real-time polymerase chain reaction. Transfection studies of bronchial epithelial cells were performed to determine the target genes. A luciferase reporter assay system was applied to identify whether Six1 is a target gene of miR-448-5p. In the current study, we found that miR-448-5p was dramatically decreased in lung tissues of asthmatic mice and TGF-ß1-stimulated bronchial epithelial cells. In addition, the decreased level of miR-448-5p was closely associated with the increased expression of Six1. Overexpression of miR-448-5p decreased Six1 expression and, in turn, suppressed TGF-ß1-mediated EMT and fibrosis. Next, we predicted that Six1 was a potential target gene of miR-448-5p and demonstrated that miR-448-5p could directly target Six1. An SiRNA targeting Six1 was sufficient to suppress TGF-ß1-induced EMT and fibrosis in 16HBE cells. Furthermore, the overexpression of Six1 partially reversed the protective effect of miR-448-5p on TGF-ß1-mediated EMT and fibrosis in bronchial epithelial cells. Taken together, the miR-448-5p/TGF-ß1/Six1 link may play roles in the progression of EMT and pulmonary fibrosis in asthma.

Downregulation of microRNA-448 inhibits IL-1ß-induced cartilage degradation in human chondrocytes via upregulation of matrilin-3.

BACKGROUND: Osteoarthritis is characterized by the continuous degradation of the articular cartilage. The microRNA miR-448 has been found to be broadly involved in cellular processes, including proliferation, apoptosis, invasion and EMT. While aberrant expression of miR-448 has been found in multiple cancers, its level in osteoarthritis cartilage and its role in the progression of this disease are still unknown. Here, we examined the functional roles of miR-448 and its expression in osteoarthritis tissues, including IL-1ß-stimulated osteoarthritis chondrocytes. METHODS: Chondrocytes were isolated from human articular cartilage and stimulated with IL-1ß. The expression levels of miR-448 in the cartilage and chondrocytes were both determined. After transfection with an miR-448 mimic or inhibitor, the mRNA levels of aggrecan, type II collagen and MMP-13 were determined. Luciferase reporter assay, qRT-PCR and western blot were performed to explore whether matrilin-3 was a target of miR-448. Furthermore, we co-transfected chondrocytes with miR-448 inhibitor and siRNA for matrilin-3 and then stimulated them with IL-1ß to determine whether miR-448-mediated IL-1ß-induced cartilage matrix degradation resulted from directly targeting matrilin-3. RESULTS: The level of miR-448 was significantly higher and matrilin-3 expression was significantly lower in osteoarthritis cartilage and IL-1ß-induced chondrocytes than in normal tissues and cells. Furthermore, matrilin-3 expression was reduced by miR-448 overexpression. MiR-448 downregulation significantly alleviated the IL-1ß-induced downregulation of aggrecan and type II collagen expression, and upregulation of MMP-13 expression. MiR-448 overexpression had the opposite effects. Knockdown of matrilin-3 reversed the effects of the miR-448 inhibitor on the expressions of aggrecan, type II collagen and MMP-13. CONCLUSION: The findings showed that miR-448 contributed to the progression of osteoarthritis by directly targeting matrilin-3. This indicates that it has potential as a therapeutic target for the treatment of osteoarthritis.

Expression of MicroRNA-448 and SIRT1 and Prognosis of Obese Type 2 Diabetic Mellitus Patients After Laparoscopic Bariatric Surgery.

BACKGROUND/AIMS: This study sought to investigate the expression and prognostic value of peripheral blood microRNA-448 (miR-448) and its target gene SIRT1 after laparoscopic bariatric surgery in obese type 2 diabetic mellitus (T2DM) patients. METHODS: Obese T2DM patients were selected and treated with laparoscopic bariatric surgery. Enzyme-linked immunosorbent assay (ELISA) was used to measure SIRT1 protein expression. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to determine the mRNA expression of the related gene. Endothelial progenitor cells (EPCs) were grouped into blank, negative control (NC), miR-448 mimic, miR-448 inhibitor, siRNA-SIRT1 and miR-448 inhibitor + siRNA-SIRT1 groups. Transwell assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were applied to determine cell invasion and cell viability. A tube formation assay and an adherence test were utilized to assess the angiogenic and adhesive capacities of the cells. RESULTS: In peripheral blood, the expression of miR-448 was reduced, whereas the mRNA and protein expression of SIRT1 was increased after surgery compared to before surgery. miR-448 expression was lower and mRNA and protein expression of SIRT1 was higher in the effective group than in the ineffective group after surgery. SIRT1 is a target gene of miR-448. miR-448 can suppress viability and invasion, and it reflects the angiogenic and adhesive capacity of EPCs and the protein expression of relative genes in EPCs through targeting SIRT1. CONCLUSION: The results demonstrated that miR-448 and its target gene SIRT1 can serve as prognostic indicators for obese T2DM patients after laparoscopic bariatric surgery.

Effect of microRNA-448 inhibitor on the proliferation and migration of human prostate cancer cells / 临床与实验病理学杂志

Purpose To observe the effect of specific miR-448 inhibitor on the proliferation and migration of prostate cancer cells and its molecular mechanism. Methods Real-time fluo-rescent quantitative polymerase chain reaction ( qRT-PCR) was used to detect the expression of miR-448 in normal prostate epi-thelial cells and cancer cells. The cells with the highest expres-sion of miR-448 were selected for follow-up experiment. The miR-448 inhibitor or miR-NC was transferred into prostate canc-er cells using liposome transfection reagent. The expression of miR-448 and CMTM3 mRNA were detected by qRT-PCR. The expression of related proteins were detected by Western blotting. MTT assay was used to detect the cell proliferation activity. Tr-answell assay was used to detect the cell migration ability. Re-sults The expression of miR-448 in normal prostate epithelial cells was significantly lower than that in cancer cells ( P ＜0. 01), and the expression of miR-448 was the highest in DU- 145 cells ( P ＜0. 01). The expression of miR-448 in DU-145 cells was down-regulated 48 h after transfection with miR-448 in-hibitor (P＜0. 01). The expression of CMTM3 mRNA was up-regulated (P＜0. 01). The expression of CMTM3, E-cadherin and β-catenin proteins were up-regulated. The expression of N-cadherin and Snail proteins were down-regulated. Cell prolifera-tion was decreased (P＜0. 05). Cell migration ability decreased (P ＜ 0. 01 ). Conclusion miR-448 is highly expressed in prostate cancer cells. miR-448 inhibitor can down-regulate the expression of miR-448 in DU-145 cells, up-regulate the expres-sion of CMTM3 protein, inhibit the proliferation and migration of prostate cancer cells, which showing a potential function in mo-lecular therapy of prostate cancer.