Circ_0003855 involvement of esophageal cancer progression through miR-622/FLOT1.

To confirm the relationship between Circ_0003855 and EC, we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC, and the expression levels of Circ_0003855, miR-622, and FLOT1 were detected. The results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells, while miR-622 was lowly expressed (p < 0.05). Subsequently, Circ_0003855 small interfering RNA (si-Circ_0003855) and its negative control (si-NC) were used to detect changes in cellular biological behaviors. We found that the activity of Eca109 cells was reduced after interfering with the expression of Circ_0003855, and miR-622 expression was elevated, while FLOT1 was decreased (p < 0.05). Additionally, si-Circ_0003855 and miR-622 inhibitor sequence (miR-622-inhibition) were co-transfected into cells with miR-622-inhibition alone, and untreated Eca109 cells were used as a control to detect the expression of FLOT1. Co-transfection of si-Circ_0003855 and miR-622-inhibition showed no significant difference in FLOT1 expression compared to the control cells (p > 0.05). Synthesizing the results of these experiments above, we believe that interfering with the expression of Circ_0003855 can inhibit the activity of EC cells, and its mechanism is related to miR-622 and FLOT1.

microRNA-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation.

BACKGROUND: Epigenetic alterations contribute greatly to the development and progression of colorectal cancer, and effect of aberrant miR-622 expression is still controversial. This study aimed to discover miR-622 regulation in CRC proliferation. METHODS: miR-622 expression and prognosis were analyzed in clinical CRC samples from Nanfang Hospital. miR-622 regulation on cell cycle and tumor proliferation was discovered, and FOLR2 was screened as functional target of miR-622 using bioinformatics analysis, which was validated via dual luciferase assay and gain-of-function and loss-of-function experiments both in vitro and in vivo. RESULTS: miR-622 overexpression in CRC indicated unfavorable prognosis and it regulated cell cycle to promote tumor growth both in vitro and in vivo. FOLR2 is a specific, functional target of miR-622, which negatively correlates with signature genes in cell cycle process to promote CRC proliferation. CONCLUSIONS: miR-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation, proposing a novel mechanism and treatment target in CRC epigenetic regulation of miR-622.

Propofol inhibits glioma progression by regulating circMAPK4/miR-622/HOXA9 axis.

Propofol has a tumor-suppressive role in glioma, but the mechanism by which propofol is involved in glioma progression is largely unknown. This study aims to explore a potential circular RNAs (circRNAs)/microRNAs (miRNAs)/mRNA network in response to Propofol in glioma. Human glioma cell lines (U251 and LN229) were suffered from Propofol treatment (5 µg/mL for 24 h) and transfection. circRNA mitogen-activated protein kinase 4 (circMAPK4), miR-622, homeobox A9 (HOXA9) abundances were determined by quantitative reverse transcription polymerase chain reaction and western blot. Migration and invasion were analyzed via transwell analysis. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation analysis. Cell apoptosis and related protein expression were determined via flow cytometry and western blot. Target relationship was assessed via dual-luciferase reporter analysis, RNA pull-down and RNA immunoprecipitation. Propofol reduced circMAPK4 expression. Propofol inhibited cell proliferation, migration and invasion, while increased apoptosis via decreasing circMAPK4 in glioma cells. miR-622 was targeted via circMAPK4. circMAPK4 knockdown decreased glioma cell growth, migration and invasion by up-regulating miR-622. miR-622 knockdown reversed the effect of Propofol on glioma progression. HOXA9 was targeted by miR-622, and its expression was decreased by Propofol treatment. miR-622 overexpression restrained glioma progression via decreasing HOXA9. Propofol regulated circMAPK4/miR-622/HOXA9 axis in glioma cells. Propofol constrains glioma progression by regulating circMAPK4/miR-622/HOXA9 axis in vitro. Propofol restrains glioma cell growth, migration and invasion. circMAPK4 can regulate HOXA9 by sponging miR-622 in glioma cells. Propofol represses glioma progression via a circMAPK4/miR-622/HOXA9 axis.

Hsa-circ-0006091 modulates the proliferation of hepatocellular carcinoma via the miR-622/CCNB1 axis.

Background/aim: Hepatocellular carcinoma (HCC) is a common type of cancer. We hypothesize that circular RNA-0006091 (circ-0006091) affects the progression of HCC. The study aims to investigate the effect of circ-0006091 in HCC cells. Materials and methods: The levels of circ-0006091, microRNA-622 (miR-622), and cyclin B1 (CCNB1) were assayed using qRT-PCR and western blotting. The metastasis of the HCC cells was measured with wound healing and transwell assays. The protein expression levels of MMP-2 and MMP-9 were assayed with western blotting. Dual-luciferase reporter and RNA-pulldown assays were used to determine the link between miR-622 and circ-0006091 or CCNB1. Mice-based tests were used to determine the effect of circ-0006091 on the proliferation of HCC cells. Results: The levels of circ-0006091 and CCNB1 were increased in the HCC cells, but miR-622 was down-regulated. Deficiency of circ-0006091 reduced the metastasis of the HCC cells, and silencing of circ-0006091 decreased the activities of MMP-2 and MMP-9 in the same cells. Circ-0006091 modulated the CCNB1 level in the HCC cells via miR-622. Silencing of circ-0006091 suppressed the proliferation of the HCC cells in vivo. Conclusion: Circ-0006091 regulated HCC cell metastasis via the miR-622/CCNB1 axis, a possible therapeutic target in managing HCC.

CircUBXN7 suppresses cell proliferation and facilitates cell apoptosis in lipopolysaccharide-induced cell injury by sponging miR-622 and regulating the IL6ST/JAK1/STAT3 axis.

Acute respiratory distress syndrome (ARDS) is a common and serious respiratory illness with substantial morbidity and mortality. Circular RNAs have been demonstrated to participate in various diseases processes. However, the biological function and mechanism of most circular RNAs have not been elucidated in ARDS. In this study, we found that circUBXN7 was significantly increased in lipopolysaccharide (LPS)-induced A549 and Beas-2B cell injury. Inhibition of circUBXN7 significantly promoted cell proliferation and reduced cell apoptosis, while overexpression of circUBXN7 suppressed cell proliferation and accelerated cell apoptosis in LPS-induced A549 and Beas-2B cells. CircUBXN7 acted as a sponge for miR-622, and miR-622 rescued the effect of circUBXN7 on cell proliferation and apoptosis. We also found that IL6ST was a target gene of miR-622, and the expression of IL6ST was indirectly regulated by circUBXN7. Furthermore, western blotting indicated that the JAK1/STAT3 signaling pathway was involved in the circUBXN7/miR-622/IL6ST axis in LPS-induced A549 and Beas-2B cell injury. Overall, our study suggested that circUBXN7 suppressed cell proliferation and facilitated cell apoptosis by sponging miR-622 and regulating IL6ST, to activate the JAK1/STAT3 signaling pathway in LPS-induced A549 and Beas-2B cell injury. CircUBXN7 might therefore be a potential biomarker for ARDS, and dysregulation of circUBXN7 may be involved in the pathogenesis of ARDS.

Circ_0005918 Sponges miR-622 to Aggravate Intervertebral Disc Degeneration.

Intervertebral discdegeneration (IDD) is the most common cause of lower back pain, but the exact molecular mechanism of IDD is still unknown. Recently, studies have shown that circular RNAs (circRNAs) regulate diverse biological procedures such as cell metastasis, growth, metabolism, migration, apoptosis, and invasion. We demonstrated that IL-1ß and TNF-α induced circ_0005918 expression in the NP cell, and circ_0005918 was overexpressed in the IDD group compared with the control group. Moreover, the upregulated expression of circ_0005918 was associated with disc degeneration degree. The elevated expression of circ_0005918 promoted cell growth and ECM degradation, and it induced secretion of inflammatory cytokines including IL-1ß, IL-6, and TNF-α. Moreover, we found that circ_0005918 sponged miR-622 in the NP cell. In addition, the exposure to IL-1ß and TNF-α suppressed the expression of miR-622, which was downregulated in the IDD group compared with the control group. Furthermore, the downregulated expression of miR-622 was associated with disc degeneration degree. The expression level of miR-622 was negatively associated with circ_0005918 expression in the IDD group. In conclusion, circ_0005918 regulated cell growth, ECM degradation, and secretion of inflammatory cytokines by regulating miR-622 expression. These data suggested that circ_0005918 played important roles in the development of IDD via sponging miR-622.

Circ_0001273 downregulation inhibits the growth, migration and glutamine metabolism of esophageal cancer cells via targeting the miR-622/SLC1A5 signaling axis.

BACKGROUND: Esophageal cancer is a relatively rare cancer. However, its death rate is not to be taken lightly. Accumulating evidence indicates circular RNA (circRNA) is implicated in cancer development. The objective of this study was to unveil the role of circ_0001273 in esophageal cancer (EC). METHODS: For expression analysis of circ_0001273, miR-622 and solute carrier family 1 member 5 (SLC1A5), quantitative real-time PCR (qPCR) and Western blot were conducted. Cell proliferation was evaluated by cell counting kit-8 (CCK-8), EdU and colony formation assays. Cell apoptosis and cell migration were investigated using flow cytometry assay and wound healing assay. Glutamine metabolism was assessed by glutamine consumption and glutamate production using matched kits. The predicted binding relationship between miR-622 and circ_0001273 or SLC1A5 was validated by dual-luciferase reporter assay. An in vivo xenograft model was established to determine the role of circ_0001273 on tumor growth. RESULTS: Circ_0001273 was upregulated in EC tumor tissues and cells. Knockdown of circ_0001273 repressed EC cell proliferation, migration, epithelial-mesenchymal transition (EMT) and glutamine metabolism. Circ_0001273 knockdown also blocked tumor development in animal models. MiR-622 was targeted by circ_0001273, and its inhibition reversed the functional effects of circ_0001273 knockdown. SLC1A5 was a target gene of miR-622, and circ_0001273 targeted miR-622 to positively regulate SLC1A5 expression. The inhibitory effects of miR-622 enrichment on EC cell proliferation, migration, EMT and glutamine metabolism were recovered by SLC1A5 overexpression. CONCLUSION: Circ_0001273 high expression contributed to EC progression via modulating the miR-622/SLC1A5 signaling axis.

Circ_KCNQ5 participates in the progression of childhood acute myeloid leukemia by enhancing the expression of RAB10 via binding to miR-622.

BACKGROUND: : Acute myeloid leukemia (AML) is regarded as a haematological malignancy and seriously threatens the public's health. Circular RNA (circRNA) is gradually confirmed to be involved in the development of AML. The purpose of this study was to disclose the role of circRNA Potassium Voltage-Gated Channel Subfamily Q Member 5 (circ_KCNQ5) in AML. METHODS: : Quantitative real-time PCR (qPCR) and western blot were used for expression analysis. Colony formation assay, EdU assay and MTT assay were performed to determine cell proliferation. Flow cytometry assay was conducted to determine cell apoptosis. The predicted binding relationship between miR-622 and circ_KCNQ5 or RAS oncogene family member 10 (RAB10) was verified by dual-luciferase reporter assay. RESULTS: : The expression of circ_KCNQ5 was increased in bone marrow samples of childhood AML patients and AML cell lines. The knockdown of circ_KCNQ5 largely suppressed AML cell proliferation and promoted cell apoptosis. Circ_KCNQ5 directly bound to miR-622 and inhibited miR-622 expression. The cotransfection of miR-622 inhibitor reversed the effects of circ_KCNQ5 knockdown and thus recovered cell proliferation and depleted cell apoptosis. RAB10 was a target of miR-622, and circ_KCNQ5 bound to miR-622 to increase the expression of RAB10. MiR-622 restoration inhibited AML cell proliferation and induced cell apoptosis, while RAB10 overexpression abolished these effects. CONCLUSION: : Circ_KCNQ5 high expression was associated with childhood AML malignant development, and circ_KCNQ5 participated in AML progression by regulating the miR-622/RAB10 pathway.

The expression and function of miR-622 in a variety of tumors.

Cancer is a heavy burden worldwide, with high morbidity and mortality rates. Cancer treatments currently involve surgical and nonsurgical approaches. Molecular targeted therapy is the latest breakthrough. miRNAs are small noncoding RNAs found in plants and animals that play a role in cancer and various diseases through influencing numerous biological processes, such as cell proliferation, apoptosis, the immune response, and drug resistance. One miRNA, miR-622, has been shown to regulate various pathways to influence disease processes. Abnormal miR-622 expression can promote or inhibit liver, colorectal, and breast cancers and other tumors, such as glioma. Herein, we reviewed the expression levels and clinical effects of miR-622 in various tumors and summarized its mechanisms and related molecules.

CircUBXN7 mitigates H/R-induced cell apoptosis and inflammatory response through the miR-622-MCL1 axis.

BACKGROUND: Hypoxia/reoxygenation (H/R)-mediated apoptosis and inflammation are major causes of tissue injury in acute myocardial infarction (AMI). Exploring the underlying mechanisms of cardiomyocyte injury induced by H/R is important for AMI treatment. Circular RNAs have been demonstrated to paly vital roles in the pathogenesis of AMI. Our study aimed to explore the function of circular RNA UBXN7 (circUBXN7) in regulating H/R-induced cardiomyocyte injury. METHODS: H/R-treated H9c2 cells and a mouse model of AMI were used to investigate the function of circUBXN7 in H/R damage and AMI. The expressions of circUNXN7, miR-622 and MCL1 were analyzed by RT-qPCR. CCK-8 was used for examining cell viability. Cell apoptosis was evaluated with caspase 3 activity and Annexin V/PI staining. MCL1, Bax, Bcl-2 and cleaved-caspase 3 were examined with western blot. ELISA was used to examine the secretion of IL-6, TNF-α and IL-1ß. RESULTS: CircUBXN7 was downregulated in patients and mice with AMI, as well as in H/R-treated cells. Overexpression of circUBXN7 mitigated H/R-mediated apoptosis and secretion of inflammatory factors including IL-6, TNF-α and IL-1ß. CircUBXN7 suppressed cell apoptosis and inflammatory reaction induced by H/R via targeting miR-622. MiR-622 targeted MCL1 to restrain its expression in H9c2 cells. Knockdown of MCL1 abrogated circUBXN7-mediated alleviation of apoptosis and inflammation after H/R treatment. CONCLUSION: CircUBXN7 mitigates cardiomyocyte apoptosis and inflammatory reaction in H/R injury by targeting miR-622 and maintaining MCL1 expression. Our study provides novel potential therapeutic targets for AMI treatment.

MiR-622 acts as a tumor suppressor to induce cell apoptosis and inhibit metastasis in human prostate cancer.

Growing evidence indicating the critical modulator roles of microRNAs (miRNAs) involved in prostate cancer (PCa) metastasis that holds great promise as therapeutic targets. Herein, we transfected the miR-622 mimic into PC3 cells and evaluated the effects of this interference on these tumour cells' growth and the expression of specific metastatic genes. Transfecting of miR-622 mimic and inhibitor, negative control (NC) inhibitor and NC was established using Lipofectamine 2000. The mRNA levels of miR-622 and metastatic genes were evaluated using the qRT-PCR and Western blot. Cytotoxic effects of miR-622 were assessed by MTT. Apoptosis was detected using an ELISA cell death assay kit. miR-622 is down-regulated in PC3 cells. As expected, cell viability effects after transfection were described as miR-622 inhibitor >NC and NC inhibitor >miR-622 mimic (p < .01). Importantly, we showed that transfected miR-622 mimic could enhance the apoptosis of PC3 cells, while transfected miR-622 inhibitor could decrease cell apoptosis (p < .01). Furthermore, miR-622 overexpression could increase significantly down-regulated the MMP2, MMP9, CXCR-4, c-Myc and K-Ras expression levels. Findings demonstrate a novel mechanism by which miR-622 modulates PCa cells' metastasis by targeting metastatic genes. These data confirm the tumour-suppressive function of miR-622 in PCa cells by enhancing apoptosis and reducing metastasis.

Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622.

BACKGROUND: Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression. METHODS: The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay. RESULTS: Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo. CONCLUSION: Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.

Combined De-Repression of Chemoresistance Associated Mitogen-Activated Protein Kinase 14 and Activating Transcription Factor 2 by Loss of microRNA-622 in Hepatocellular Carcinoma.

Chemoresistance is a major hallmark driving the progression and poor prognosis of hepatocellular carcinoma (HCC). Limited chemoresponse of HCC was demonstrated to be mediated by mitogen-activated protein kinase 14 (MAPK14) and activating transcription factor 2 (ATF2). Recently, we have demonstrated loss of control of RAS-RAF-ERK-signaling as a consequence of miR-622 downregulation in HCC. However, the majority of target genes of this potent tumorsuppressive microRNA had remained elusive. The MAPK14-ATF2-axis represents a collateral pathway ensuring persisting ERK-activation in the presence of sorafenib-mediated RAF-inhibition. In contrast to the function of the MAPK14-ATF2-axis, both the expression and regulation of MAPK14 and ATF2 in human HCC remained to be clarified. We found combined overexpression of MAPK14 and ATF2 in human HCC cells, tissues and in sorafenib resistant cell lines. High expression of MAPK14 and ATF2 was associated with reduced overall survival in HCC patients. Deciphering the molecular mechanism promoting combined upregulation of MAPK14 and ATF2 in HCC, we revealed that miR-622 directly targets both genes, resulting in combined de-repression of the MAPK14-ATF2-axis. Together, miR-622 represents a superior regulator of both RAS-RAF-ERK as well as MAPK14-ATF2-signaling pathways in liver cancer.

A Circular RNA Derived from Golgi Glycoprotein 1 mRNA Regulates KRAS Expression and Promotes Colorectal Cancer Progression by Targeting microRNA-622.

BACKGROUND: Circular RNAs (circRNAs) represent a distinct class of non-coding RNAs that have attracted substantial research attention in recent years. We identified a novel circRNA derived from golgi glycoprotein 1 mRNA (circ_GLG1), the role of which is unknown in colorectal cancer (CRC). The purpose of this study was to explore the potential roles and mechanisms of circ_GLG1 in CRC. MATERIALS AND METHODS: Quantitative reverse transcriptase-polymerase chain reaction analysis was performed to quantify circ_GLG1 expression in 40 pairs of CRC tissues and adjacent normal tissues as well as CRC cell lines. DLD1 CRC cells were transfected with a small-interfering RNA against circ_GLG1, after which cell proliferation, viability, invasion, and migration were measured through cell counting kit-8 colony-formation, transwell, and wound-healing assays, respectively. Dual-luciferase reporter assays were performed to explore the binding sites among circ_GLG1, miR-622, and Kirsten rat sarcoma (KRAS) transcripts. KRAS protein expression was detected using Western blot analysis. RESULTS: Circ_GLG1 expression was significantly higher in CRC tissues than in adjacent normal tissues. Knocking down circ_GLG1 in DLD1 cells inhibited tumor cell viability, proliferation, invasion, and migration, and these effects were reversed by co-transfecting an miR-622 inhibitor. Circ_GLG1 promoted KRAS expression at both the mRNA and protein levels by acting as an miR-622 sponge. Dual-luciferase reporter assays demonstrated that miR-622 interacted with circ_GLG1 and KRAS mRNA. CONCLUSION: Our study revealed the role of the circ_GLG1-miR-622-KRAS axis in CRC. Moreover, our findings provide insight into the molecular mechanism of circ_GLG1 in CRC and suggest potential new biomarkers for diagnosing this disease.

Silencing of circular RNA ANRIL attenuates oxygen-glucose deprivation and reoxygenation-induced injury in human brain microvascular endothelial cells by sponging miR-622.

BACKGROUND: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury. RESULTS: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-κB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. CONCLUSIONS: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.

Tumor-associated exosomal miRNA biomarkers to differentiate metastatic vs. nonmetastatic non-small cell lung cancer.

Background: Exosomal microRNAs (miRNAs) are proposed to be excellent candidate biomarkers for clinical applications. However, little is known about their potential value as diagnostic biomarkers for metastatic non-small cell lung cancer (NSCLC). Methods: In this study, microarrays were used to determine distinct miRNA profiles of plasma exosomes in a discovery cohort of healthy donors, metastatic NSCLC and nonmetastatic NSCLC patients. Three potential candidate miRNAs were selected based on the differential expression profiles. The discovery set data were validated by quantitative real-time polymerase chain reaction using a validation cohort. Results: NSCLC patients (n = 80) and healthy controls (n = 30) had different exosome-related miRNA profiles in plasma. Results demonstrated that the level of let-7f-5p was decreased in plasma exosomes of NSCLC patients (p < 0.0001). Further analysis of three differentially expressed miRNAs revealed that miR-320a, miR-622 and let-7f-5p levels could significantly segregate patients with metastatic NSCLC from patients with nonmetastatic NSCLC (p < 0.0001, p < 0.0001 and p = 0.023, respectively). In addition, the combination of let-7f-5p, CEA and Cyfra21-1 generated an area under the curve (AUC) of 0.981 for the diagnosis of NSCLC patients, and the combination of miR-320a, miR-622, CEA and Cyfra21-1 had an AUC of 0.900 for the diagnosis of patients with metastatic NSCLC. Conclusions: This novel study demonstrated that plasma exosomal miRNAs are promising noninvasive diagnostic biomarkers for metastatic NSCLC.

Genetic Analysis of Ulcerative Colitis in Japanese Individuals Using Population-specific SNP Array.

BACKGROUND: To clarify the genetic background of ulcerative colitis (UC) in the Japanese population, we conducted a genome-wide association study (GWAS) using a population-specific single nucleotide polymorphism (SNP) array. METHODS: We performed a GWAS and replication study including 1676 UC patients and 2381 healthy controls. The probability of colectomy was compared between genotypes of rs117506082, the top hit SNP at HLA loci, by the Kaplan-Meier method. We studied serum expression of miR-622, a newly identified candidate gene, from 32 UC patients and 8 healthy controls by quantitative reverse-transcription polymerase chain reaction. RESULTS: In the GWAS, only the HLA loci showed genome-wide significant associations with UC (rs117506082, P = 6.69E-28). Seven nominally significant regions included 2 known loci, IL23R (rs76418789, P = 6.29E-7) and IRF8 (rs16940202, P = 1.03E-6), and 5 novel loci: MIR622 (rs9560575, P = 8.23E-7), 14q31 (rs117618617, P = 1.53E-6), KAT6B (rs12260609, P = 1.81E-6), PAX3-CCDC140-SGPP2 (rs7589797, P = 2.87E-6), and KCNA2 (rs118020656, P = 4.01E-6). Combined analysis revealed that IL23R p.G149R (rs76418789, P = 9.03E-11; odds ratio [OR], 0.51) had genome-wide significant association with UC. Patients with GG genotype of rs117506082 had a significantly lower probability of total colectomy than those with the GA+AA genotype (P = 1.72E-2). Serum expression of miR-622 in patients with inactive UC tended to be higher than in healthy controls and patients with active UC (inactive UC vs healthy controls, P = 3.03E-02; inactive UC vs active UC, P = 6.44E-02). CONCLUSIONS: IL23R p.G149R is a susceptibility locus for UC in Japanese individuals. The GG genotype of rs117506082 at HLA loci may predict a better clinical course.

Predictive Relevance of Circulating miR-622 in Patients with Newly Diagnosed and Recurrent High-Grade Serous Ovarian Carcinoma.

BACKGROUND: Identifying patients with high-grade serous ovarian cancer (HGSOC) who will respond to treatment remains a clinical challenge. We focused on miR-622, a miRNA involved in the homologous recombination repair (HRR) pathway, and we assessed its predictive value in serum prior to first-line chemotherapy and at relapse. METHODS: Serum miR-622 expression was assessed in serum prior to first-line platinum-based chemotherapy in a prospective multicenter study (miRNA Serum Analysis, miRSA, NCT01391351) and a retrospective cohort (Biological Resource Center, BRC), and was also studied at relapse. Progression-free survival (PFS) and overall survival (OS) were used as primary and secondary endpoints prior to first-line chemotherapy and OS as a primary endpoint at relapse. RESULTS: The group with high serum miR-622 expression was associated with a significantly lower PFS (15.4 versus 24.4 months; adjusted HR 2.11, 95% CI 1.2 3.8, P = 0.015) and OS (29.7 versus 40.6 months; adjusted HR 7.68, 95% CI 2.2-26.2, P = 0.0011) in the miRSA cohort. In the BRC cohort, a high expression of miR-622 was also associated with a significantly lower OS (22.8 versus 35.9 months; adjusted HR 1.98, 95% CI 1.1-3.6, P = 0.026). At relapse, high serum miR-622 was associated with a significantly lower OS (7.9 versus 20.6 months; adjusted HR 3.15, 95% CI 1.4-7.2, P = 0.0062). Serum miR-622 expression is a predictive independent biomarker of response to platinum-based chemotherapy for newly diagnosed and recurrent HGSOC. CONCLUSIONS: These results may open new perspectives for HGSOC patient stratification and monitoring of resistance to platinum-based and poly(ADP-ribose)-polymerase-inhibitor-maintenance therapies, facilitating better and personalized treatment decisions.

Dissimilar Appearances Are Deceptive-Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma.

: In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs-melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these-at first sight-dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

A novel circular RNA, hsa-circ-0000211, promotes lung adenocarcinoma migration and invasion through sponging of hsa-miR-622 and modulating HIF1-α expression.

Recently, several studies have evaluated the role of circular RNAs in the metastasis and development of multiple cancers. In our earlier microarray-based study, we had reported the aberrant expression of a novel circular RNA, hsa-circ-0000211 in lung adenocarcinoma (LAC) tissues. However, the roles of hsa-circ-0000211 in LAC have not been studied. Here hsa-circ-0000211 expression in the LAC tissues and cell lines was determined by quantitative real-time PCR (qRT-PCR). The function of hsa-circ-0000211 was evaluated by transwell assay and wound healing. Mechanisms of hsa-circ-0000211 was measured by luciferase reporter assay and western blot. Results revealed the expression of hsa-circ-0000211 in the human LAC tissues and LAC cell lines was higher than that in normal tissue and human lung normal epithelial cells, respectively. The knockdown of hsa-circ-0000211 could inhibit the migration and invasion properties of LAC. Furthermore, hsa-circ-0000211 promoted the migration and invasion of LAC by sponging miR-622. Moreover, hsa-circ-0000211 upregulated the HIF1-α expression by targeting miR-622. hsa-circ-0000211 promoted LAC cell migration and invasion by modulating the miR-622/HIF1-α network. Our study demonstrated that hsa-circ-0000211 can be a potential novel therapeutic target for LAC.