MicroRNA-204-5p Hampers the Malignant Progression of Clear Cell Renal Cell Carcinoma through GXYLT2 Downregulation.

INTRODUCTION: At present, the mortality rate of clear cell renal cell carcinoma (ccRCC) remains high. The development of biomarkers is conducive to the early diagnosis and treatment of cancer. This research aimed to explore the role of microRNA-204-5p and the downstream gene in ccRCC. METHODS: We used bioinformatics analysis and qRT-PCR for measurement of microRNA-204-5p, qRT-PCR, and Western blot for GXYLT2 mRNA and protein levels, respectively. We conducted in vitro experiments like CCK-8, colony formation, Transwell, wound healing, and cell cycle assays to assess the role of microRNA-204-5p and GXYLT2 in ccRCC. Besides, the target relationship of microRNA-204-5p and GXYLT2 was confirmed through dual-luciferase assay. RESULTS: This study disclosed that microRNA-204-5p was underexpressed in ccRCC cells and tissues, which was closely associated with prognosis of patients with ccRCC. Stable forced expression of microRNA-204-5p hindered malignant phenotypes of ccRCC cells. Further detection unfolded that micro-RNA-204-5p bound the 3'-UTR of GXYLT2 to repress its expression. Besides, forced expression of microRNA-204-5p restored the promoting impact of overexpression of GXYLT2 on malignant progression of ccRCC cells. CONCLUSION: These findings revealed the vital role of microRNA-204-5p and GXYLT2 in ccRCC progression, as well as the possibility of microRNA-204-5p in improving ccRCC prognosis and treatment.

Long noncoding MIAT acting as a ceRNA to sponge microRNA-204-5p to participate in cerebral microvascular endothelial cell injury after cerebral ischemia through regulating HMGB1.

This study is applied to the investigation of the long noncoding RNA myocardial infarction associated transcript's (MIAT's) role in regulating the expression of high-mobility group box 1 (HMGB1) in cerebral microvascular endothelial cell (CMEC) injury after cerebral ischemia by serving as a competitive endogenous RNA (ceRNA) to sponge microRNA-204-5p (miR-204-5p). The cerebral ischemia model of middle cerebral artery occlusion (MCAO) in rats was established by the suture method, in which rats were injected with empty plasmids and MIAT siRNA plasmids. The cerebral ischemia injury model in vitro was established through oxygen glucose deprivation (OGD) in primary cultured CMECs in rats. The cells were transfected with empty plasmids and MIAT siRNA plasmids. The MIAT/miR-204-5p/HMGB1 axis' function in damage and angiogenesis of CMECs were explored. The binding site between MIAT and miR-204-5p along with that between miR-204-5p and HMGB1 was determined. MIAT was overexpressed in MCAO rats' brain tissue and inhibited MIAT attenuated the injury of brain tissue in MCAO rats. Inhibition of MIAT promoted angiogenesis, promoted miR-204-5p expression and inhibited HMGB1 expression in brain tissue of MCAO rats. Inhibition of MIAT reduced CMEC damage, induced angiogenesis of CMECs, increased the number of surviving neurons, promoted miR-204-5p expression and inhibited HMGB1 expression in CMECs treated with OGD. MIAT promoted HMGB1 expression by competitive binding to miR-204-5p to regulate the injury of CMECs after cerebral ischemia. Our study showed that MIAT promoted HMGB1 expression by competitively binding to miR-204-5p to regulate the injury of CMECs after cerebral ischemia.

Overexpression of microRNA-204-5p alleviates renal ischemia-reperfusion injury in mice through blockage of Fas/FasL pathway.

The multiple roles of microRNA-204-5p (miR-204-5p) in numerous types of cancer have been reported, but its function in renal ischemia-reperfusion injury (RIRI) remains unclear. In this study, we aim to explore whether miR-204-5p was implicated in the RIRI in mice via regulating the Fas/Fas ligand (FasL) pathway. Firstly, the Gene Expression Omnibus (GEO) database was used to screen RIRI-related differentially expressed genes (DEGs). Then, RIRI mouse model was established, and the role of miR-204-5p and FasL in RIRI was explored by ectopic expression, depletion and reporter assay experiments. The blood urea nitrogen (BUN) and serum creatinine (Scr) levels in serum, as well as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in renal tissues of mice were also measured. Afterwards, the regulatory role of miR-204-5p on Fas/FasL pathway in RIRI was investigated. Renal tissues from RIRI mice showed lower miR-204-5p expression and higher Fas and FasL expression. FasL was identified as a direct target gene of miR-204-5p. In addition, the increased levels of BUN, Scr and MDA, as well as decreased levels of SOD and GSH-Px in RIRI mice were reversed by elevation of miR-204-5p and blockage of the Fas/FasL pathway. Taken together, this study demonstrated that increased miR-204-5p might suppress RIRI in mice through suppressing Fas/FasL pathway by targeting FasL.

MicroRNA-204-5p suppresses IL6-mediated inflammatory response and chemokine generation in HK-2 renal tubular epithelial cells by targeting IL6R.

During the pathogenetic process of varied kidney diseases, renal tubules are the major sites in response to detrimental insults, including pro-inflammatory stimuli. MicroRNA-204-5p (miR-204-5p) can be detected in the renal tubular epithelial cells in the normal kidney; its expression, however, is downregulated in the kidney with pathological changes. This study aimed to investigate the role of miR-204-5p in interleukin 6 (IL6) mediated inflammatory response and chemokine production in HK-2 renal tubular cells. In HK-2 cells, the expression of miR-204-5p was downregulated in response to exogenous pro-inflammatory stimulus, tumor necrosis factor α (TNFα), or IL1ß, while that of IL6 receptor α (IL6R) was upregulated. Dual-luciferase results confirmed that miRNA-204-5p directly targeted IL6R. In addition to suppressing IL6R expression, miRNA-204-5p agomir also inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in HK-2 cells exposed to exogenous IL6. Further, miRNA-204-5p suppressed the overproduction of pro-inflammatory mediators (cyclooxygenase 2 and prostaglandin E2) and chemokines (C-C motif chemokine ligand 2 and C-X-C motif chemokine ligand 8). The anti-inflammatory effects of miRNA-204-5p were attenuated when IL6R was reexpressed in HK-2 cells. Collectively, our study reveals that miR-204-5p inhibits the inflammation and chemokine generation in renal tubular epithelial cells by modulating the IL6/IL6R axis.

Tumor-Derived Exosomal LINC01480 Upregulates VCAM1 Expression by Acting as a Competitive Endogenous RNA of miR-204-5p to Promote Gastric Cancer Progression.

Exosomes are a type of cell-derived vesicles that range in size from 30 to 100 nm. They are widely present in various organisms and participate in diverse biological processes, playing crucial roles in tumorigenesis and progression. This study aimed to investigate whether LINC01480 in tumor-derived exosomes is involved in the molecular mechanism of gastric cancer by competitively upregulating the VCAM1 expression through binding miR-204-5p. The study analyzed transcriptome data related to gastric cancer from the cancer genome atlas database and constructed a risk-scoring model for epithelial-mesenchymal transition (EMT)-related lncRNAs to identify eight EMT-related lncRNAs associated with prognosis. EMT-related mRNAs positively correlated with LINC01480 were screened in the ExoRBase database. In vitro cell experiments showed that exosomal LINC01480 can promote the proliferation, migration, invasion, and EMT of gastric cancer cells by upregulating VCAM1 expression through competitive binding with miR-204-5p. In vivo experiments on nude mice showed that exosomal LINC01480 promotes the development of gastric cancer. These results suggest that exosomal LINC01480 could be a potential therapeutic target for gastric cancer.

MicroRNA-204-5p Ameliorates Neurological Injury via the EphA4/PI3K/AKT Signaling Pathway in Ischemic Stroke.

Ischemic stroke has extremely high mortality and disability rates worldwide. miR-204-5p has been reported to be associated with neurological diseases. However, the relationship linking miR-204-5p to ischemic stroke and its molecular mechanism remain unclear. Herein, we found that expression of miR-204-5p was significantly decreased while EphA4 increased in vivo and vitro, which reached the peak at 24 h after cerebral ischemia/reperfusion. Then, we altered miR-204-5p expression in rats by cerebroventricular injection. Our study showed that miR-204-5p overexpression obviously reduced the brain infarction area and neurological score. We successfully cultured neurons to investigate the downstream mechanism. Upregulation of miR-204-5p increased cell viability and suppressed the release of LDH. Moreover, the proportion of apoptotic cells tested by TUNEL and flow cytometry and protein expression of Cleaved Caspase3 and Bax were inhibited. The relative expression of IL-6, TNF-α, and IL-1ß was repressed. In contrary, knockdown of miR-204-5p showed the opposite results. Bioinformatics and a dual luciferase assay illustrated that EphA4 was a target gene. Further research studies demonstrated that the neuroprotective effects of miR-204-5p could be partially mitigated by upregulating EphA4. Next, we proved that the miR-204-5p/EphA4 axis furtherly activated the PI3K/AKT pathway. We thoroughly illustrated the role of neuroinflammation and apoptosis. However, whether there are other mechanisms associated with the EphA4/PI3K/AKT pathway needs further investigation. Altogether, the miR-204-5p axis ameliorates neurological injury via the EphA4/PI3K/AKT pathway, which is expected to serve as an effective treatment for ischemic stroke.

NDRG3 regulates imatinib resistance by promoting ß­catenin accumulation in the nucleus in chronic myelogenous leukemia.

Imatinib resistance in chronic myelogenous leukemia (CML) is a clinical problem. The present study examined the role of N­Myc downstream regulatory gene 3 (NDRG3) in imatinib resistance in CML. Quantitative PCR demonstrated that NDRG3 was highly expressed in patients with CML. Cell Counting Kit (CCK)­8 experiments proved that NDRG3 promoted the proliferation of K562 CML cells and enhanced imatinib resistance. Dual­luciferase assay showed that microRNA (miR)­204­5p inhibited expression of NDRG3 and immunofluorescence experiments showed that NDRG3 promoted accumulation of ß­catenin in the nucleus, thereby increasing the expression of downstream drug resistance­ and cell cycle­associated factors (c­Myc and MDR1). At the same time, cell proliferation experiments showed that ß­catenin played a role in cell proliferation and drug resistance. Co­transfection with small interfering (si)­ß­catenin partially reversed the effect of NDRG3. This finding indicated that NDRG3 plays an important role in imatinib resistance and miR­204­5p and ß­catenin are involved in the biological behavior of NDRG3. The present results provide theoretical support for overcoming drug resistance in CML.

MicroRNA-204/CREB5 axis regulates vasculogenic mimicry in breast cancer cells.

BACKGROUND: Vasculogenic mimicry (VM) is characterized by formation of three-dimensional (3D) channels-like structures by tumor cells, supplying the nutrients needed for tumor growth. VM is stimulated by hypoxic tumor microenvironment, and it has been associated with increased metastasis and clinical poor outcome in cancer patients. cAMP responsive element (CRE)-binding protein 5 (CREB5) is a hypoxia-activated transcription factor involved in tumorigenesis. However, CREB5 functions in VM and if its regulated by microRNAs remains unknown in breast cancer. OBJECTIVE: We aim to study the functional relationships between VM, CREB5 and microRNA-204-5p (miR-204) in breast cancer cells. METHODS: CREB5 expression was evaluated by mining the public databases, and using RT-qPCR and Western blot assays. CREB5 expression was silenced using short-hairpin RNAs in MDA-MB-231 and MCF-7 breast cancer cells. VM formation was analyzed using matrigel-based cultures in hypoxic conditions. MiR-204 expression was restored in cancer cells by transfection of RNA mimics. Luciferase reporter assays were performed to evaluate the binding of miR-204 to 3'UTR of CREB5. RESULTS: Our data showed that CREB5 mRNA expression was upregulated in a set of breast cancer cell lines and clinical tumors, and it was positively associated with poor prognosis in lymph nodes positive and grade 3 basal breast cancer patients. Silencing of CREB5 impaired the hypoxia-induced formation of 3D channels-like structures representative of the early stages of VM in MDA-MB-231 cells. In contrast, VM formation was not observed in MCF-7 cells. Interestingly, we found that CREB5 expression was negatively regulated by miR-204 mimics in breast cancer cells. Functional analysis confirmed that miR-204 binds to CREB5 3'-UTR indicating that it's an ulterior effector. CONCLUSIONS: Our findings suggested that CREB5 could be a potential biomarker of disease progression in basal subtype of breast cancer, and that perturbations of the miR-204/CREB5 axis plays an important role in VM development in breast cancer cells.

lncRNA SNHG4 promotes cell proliferation, migration, invasion and the epithelial-mesenchymal transition process via sponging miR-204-5p in gastric cancer.

Long non­coding (lnc)RNAs and microRNAs (miRNAs/miRs) have physiological and pathological functions in various diseases, including gastric cancer (GC). The current study explored the association between lncRNA small nucleolar RNA host gene 4 (SNHG4) and miR­148a­3p, and their functions in GC cells. SNHG4 expression and overall survival data were analyzed using bioinformatics, and the interaction of SNHG4 and miR­148a­3p was predicted using starBase and confirmed via a dual­luciferase reporter assay. Cell viability, colony formation ability and apoptosis rate were detected using Cell Counting Kit­8, colony formation and flow cytometry assays, respectively. Cell migration and invasion were determined via wound­healing and Transwell assays. mRNA and protein expression levels were determined via reverse transcription­quantitative PCR and western blotting. The results demonstrated that in GC tissues and cell lines, SNHG4 was highly expressed, while miR­204­5p expression was decreased, and that the expression levels of SNHG4 and miR­204­5p were negatively correlated. The downregulated expression of SNHG4 decreased the effects of miR­204­5p inhibitor on promoting cell proliferation, migration, invasion and epithelial­mesenchymal transition, but enhanced the inhibitory effect of miR­204­5p on GC cell apoptosis. The findings of the current study revealed the potential mechanism of the SNHG4­miR­204­5p pathway in GC, which may be conducive to the development of novel drugs against GC growth.

Long non-coding RNA KCNQ1OT1/microRNA-204-5p/LGALS3 axis regulates myocardial ischemia/reperfusion injury in mice.

Myocardial ischemia/reperfusion (IR) injury is one of the most prevalent cardiovascular diseases, known for its high mortality and morbidity worldwide. Based on pre-existing evidence, LGALS3 has been found to be closely associated with cardiac diseases. Hence, the objective of our study is to explore the potential function of KCNQ1OT1/microRNA-204-5p (miR-204-5p)/ LGALS3 axis on myocardial IR injury and the underlying mechanism. A myocardial IR injury mouse model was established in vivo and an in vitro cardiomyocyte model was induced by hypoxia/Reoxygenation exposure. Next, gain- and loss-of-function experiments were employed in order to measure the viability and apoptosis of cardiomyocytes and the area of ischemic infarct by CCK-8, TUNEL staining and Evans blue/TTC double staining. LGALS3 was found to be highly expressed in myocardial IR injury. The downregulation of LGALS3 resulted in the alleviation of myocardial IR injury in mouse models. In addition, KCNQ1OT1 could promote the LGALS3 expression by binding to miR-204-5p, which led to aggravated myocardial IR injury. In conclusion, KCNQ1OT1 binds to miR-204-5p to exacerbate myocardial IR injury in mice through the up-regulation of LGALS3, providing a novel insight for myocardial IR injury treatment.

miR­204­5p promotes apoptosis and inhibits migration of gastric cancer cells by targeting HER­2.

Gastric cancer is one of the most common types of cancer worldwide, with a high incidence and mortality rate. MicroRNAs (miRs) play an important role in tumorigenesis, cell proliferation, migration, apoptosis and metastasis of cancer. The present study aimed to investigate the role and potential mechanism of miR­204­5p in gastric cancer. The mRNA expression levels of miR­204­5p in gastric cancer were determined by reverse transcription­quantitative PCR. Cell proliferation was determined using Cell Counting Kit­8 and colony formation assays. Flow cytometry analysis was performed to detect the cell apoptosis rate. Wound healing and Transwell assays were carried out to determine the cell migration and invasion rates, respectively. A putative binding site of miR­204­5p in the 3' untranslated region of human epidermal growth factor receptor 2 (HER­2) was predicted using a bioinformatics algorithm and confirmed using a dual­luciferase reporter assay. miR­204­5p levels were downregulated in gastric cancer cells. Overexpression of miR­204­5p significantly inhibited cell proliferation and decreased cell colony formation. Additionally, miR­204­5p decreased the migration and invasion rates of gastric cancer cells. Furthermore, an increased apoptotic rate was detected following overexpression of miR­204­5p, along with increased expression levels of Bax and decreased expression levels of Bcl­2. HER­2 was a direct target of miR­204­5p, and inhibition of HER­2 acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis, which was reversed by the inhibition of miR­204­5p expression. These results suggested that miR­204­5p could exert its anti­tumor function by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis via regulation of HER­2, which may be a potential therapeutic target for gastric cancer.

Long non-coding RNA OIP5-AS1 serves as an oncogene in laryngeal squamous cell carcinoma by regulating miR-204-5p/ZEB1 axis.

Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer with poor prognosis. In the present study, we aimed to investigate the biological role of long non-coding RNA OIP5-AS1 in LSCC. The results demonstrated that the expression levels of OIP5-AS1 were significantly increased in LSCC tissues and cell lines. High expression of OIP5-AS1 was closely correlated with lymph node metastasis and advanced clinical stage of LSCC patients. Moreover, in vitro assays showed that OIP5-AS1 overexpression promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of LSCC cells, whereas OIP5-AS1 knockdown exerted suppressive effects on LSCC cells. Furthermore, OIP5-AS1 was confirmed to serve as a competing endogenous RNA of miR-204-5p in LSCC cells, and restoration of miR-204-5p counteracted the OIP5-AS1-mediated oncogenic effects. In conclusion, our study provides promising evidence that lncRNA OIP5-AS1 functions as a tumor promoter in LSCC and may be used as a potential target for LSCC therapy.

miR-204-5p promotes diabetic retinopathy development via downregulation of microtubule-associated protein 1 light chain 3.

Diabetic retinopathy (DR) is a chronic and progressive complication of diabetes mellitus. DR impairs sight due to neuronal and vascular dysfunction in the retina. It is critical to investigate the pathogenesis of DR to develop effective treatment. In the present study, a streptozotocin (STZ)-induced diabetic rat model was constructed and the expression of microRNA (miR)-204-5p and vascular endothelial growth factor (VEGF) were determined. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were employed to detect the effects of miR-204-5p on the expression of microtubule-associated protein 1 light chain 3 (LC3B). RT-qPCR analysis demonstrated that miR-204-5p and VEGF were significantly upregulated in the retina tissue of diabetic rats compared with the control group (P<0.01). Immunohistochemistry and western blotting revealed that the protein expression levels of LC3B-II and the ratio of LC3B-II/LC3B-I were significantly suppressed in the diabetes group compared with the control (P<0.01). In retinal tissues, anti-miR-204-5p treatment significantly enhanced the protein expression levels of LC3B-II and the ratio of LC3B-II/LC3B-I and these levels were significantly reduced in response to miR-204-5p mimic treatment compared with the negative miR control (P<0.01). In rat retinal endothelial cells isolated from diabetic rats, anti-miR-204-5p treatment increased the number of autophagic vacuoles, and significantly promoted LC3B-II expression and the LC3B-II/LC3B-I ratio compared with the negative control (P<0.01). The results of the present study revealed that miR-204-5p downregulated the expression of LC3B-II to inhibit autophagy in DR. Therefore, miR-204-5p may be considered as a novel effective therapeutic target during the development of DR.

Upregulated Expression of MicroRNA-204-5p Leads to the Death of Dopaminergic Cells by Targeting DYRK1A-Mediated Apoptotic Signaling Cascade.

MicroRNAs (miRs) downregulate or upregulate the mRNA level by binding to the 3'-untranslated region (3'UTR) of target gene. Dysregulated miR levels can be used as biomarkers of Parkinson's disease (PD) and could participate in the etiology of PD. In the present study, 45 brain-enriched miRs were evaluated in serum samples from 50 normal subjects and 50 sporadic PD patients. The level of miR-204-5p was upregulated in serum samples from PD patients. An upregulated level of miR-204-5p was also observed in the serum and substantia nigra (SN) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Expression of miR-204-5p increased the level of α-synuclein (α-Syn), phosphorylated (phospho)-α-Syn, tau, or phospho-tau protein and resulted in the activation of endoplasmic reticulum (ER) stress in SH-SY5Y dopaminergic cells. Expression of miR-204-5p caused autophagy impairment and activation of c-Jun N-terminal kinase (JNK)-mediated apoptotic cascade in SH-SY5Y dopaminergic cells. Our study using the bioinformatic method and dual-luciferase reporter analysis suggests that miR-204-5p positively regulates mRNA expression of dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) by directly interacting with 3'UTR of DYRK1A. The mRNA and protein levels of DYRK1A were increased in SH-SY5Y dopaminergic cells expressing miR-204-5p and SN of MPTP-induced PD mouse model. Knockdown of DYRK1A expression or treatment of the DYRK1A inhibitor harmine attenuated miR-204-5p-induced increase in protein expression of phospho-α-Syn or phospho-tau, ER stress, autophagy impairment, and activation of JNK-mediated apoptotic pathway in SH-SY5Y dopaminergic cells or primary cultured dopaminergic neurons. Our results suggest that upregulated expression of miR-204-5p leads to the death of dopaminergic cells by targeting DYRK1A-mediated ER stress and apoptotic signaling cascade.

Expression and potential molecular mechanisms of miR­204­5p in breast cancer, based on bioinformatics and a meta­analysis of 2,306 cases.

Breast cancer (BC) is the most common cancer among women worldwide. However, there is insufficient research that focuses on the expression and molecular mechanisms of microRNA (miR)­204­5p in BC. In the current study, data were downloaded from the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and the University of California Santa Cruz (UCSC) Xena databases. They were then used to undertake a meta­analysis that leveraged the standard mean difference (SMD) and summarized receiver operating characteristic (sROC) to evaluate the expression of the precursor miR­204 and mature miR­204­5p in BC. Additionally, an intersection of predicted genes, differentially expressed genes (DEGs) from the TCGA database and the GEO database were plotted to acquire desirable putative genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein­protein interaction (PPI) network analyses were performed to assess the potential pathways and hub genes of miR­204­5p in BC. A decreased trend in precursor miR­204 expression was detected in 1,077 BC tissue samples in comparison to 104 para­carcinoma tissue samples in the TCGA database. Further, the expression of mature miR­204­5p was markedly downregulated in 756 BC tissue samples in comparison to 76 para­carcinoma tissue samples in the UCSC Xena database. The outcome of the SMD from meta­analysis also indicated that the expression of miR­204­5p was markedly reduced in 2,306 BC tissue samples in comparison to 367 para­carcinoma tissue samples. Additionally, the ROC and sROC values indicated that miR­204­5p had a great discriminatory capacity for BC. In GO analysis, 'cell development', 'cell surface activity', and 'receptor agonist activity' were the most enriched terms; in KEGG analysis, 'endocytosis' was significantly enriched. Rac GTPase activating protein 1 (RACGAP1) was considered the hub gene in the PPI network. In conclusion, miR­204­5p may serve a suppressor role in the oncogenesis and advancement of BC, and miR­204­5p may have crucial functions in BC by targeting RACGAP1.

Circular RNA PVT1 promotes the invasion and epithelial-mesenchymal transition of breast cancer cells through serving as a competing endogenous RNA for miR-204-5p.

PURPOSE: Circular RNAs (circRNAs) are a class of covalently closed circular RNA transcripts and have been found to regulate the progression of human malignancies. The objective of this study was to identify the functions of circRNAs in breast cancer (BCa). PATIENTS AND METHODS: BCa and adjacent non-cancerous tissues were collected from 99 patients. Kaplan-Meier analysis was used to analyze the relationship between circPVT1 and prognosis. CircPVT1 expression levels in BCa tissues and cell lines were detected via PCR. Transfection technology was used to silence circPVT1 and overexpress miR-204-5p. Cell biological behavior was analyzed, and epithelial-mesenchymal transition (EMT) related proteins were detected by Western blot. In vivo experiments were performed with the subcutaneous xenograft tumor model. RESULTS: CircPVT1 was markedly overexpressed in BCa tissues and cell lines. Higher expression of circPVT1 was correlated with poor prognosis of BCa patients. Knockdown circPVT1 significantly suppressed the proliferation, migration and invasion of BCa cells invitro, and suppressed BCa tumor growth invivo. CircPVT1 knockdown upregulated E-cadherin and downregulated N-cadherin, Vimentin, Slug and Twist in BCa cells. Moreover, circPVT1 could serve as a competing endogenous RNA (ceRNA) for miR-204-5p, and restoration of miR-204-5p abrogated the oncogenic role of circPVT1 in BCa cells. CONCLUSION: CircPVT1 as a potentially valuable biomarker for BCa diagnosis and therapeutic target for BCa treatment. CircPVT1 might promote the invasion and EMT of BCa cells by serving as aceRNA for miR-204-5p.

miR-204-5p and miR-3065-5p exert antitumor effects on melanoma cells.

MicroRNA (miR)-204-5p was previously identified to be downregulated in melanoma compared with melanocytic nevi. This observation prompted a functional study on miR-204-5p and the newly-identified miR-3065-5p, two miRNAs suggested to be tumor-suppressive oncomiRs. Application of miR-204-5p mimics or inhibitors resulted in a decrease or increase, respectively, in melanoma cell proliferation and colony formation. miR-204-5p mimics hindered invasion, whereas miR-204-5p inhibitors stimulated cancer cell migration. Modulation of miR-3065-5p led to a decrease in melanoma cell proliferation, altered cell cycle distribution and increased expression levels of its target genes HIPK1 and ITGA1, possibly due to functional modifications identified in these cells. miR-204-5p and miR-3065-5p demonstrated antitumor capacities that may need to be taken into account in the development of melanoma treatment approaches.