Circular RNA circUBE2J2 acts as the sponge of microRNA-370-5P to suppress hepatocellular carcinoma progression

Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular carcinoma is largely unknown. CircRNA microarray was performed to identify abnormally expressed circRNAs in HCC tissue samples. We conducted Kaplan–Meier survival analysis to explore the significance of circUBE2J2 in clinical prognosis. Then, we examined the functions of circUBE2J2 in HCC by cell proliferation, migration, and mouse xenograft assay. We identified miR-370-5P as a circUBE2J2-related microRNA by using biotin-labeled circUBE2J2 probe to perform RNA antisense purification (RAP) assay in HCC cells. The dual luciferase reporter assay and RNA pulldown assays were employed to verify the relationships among circUBE2J2, miRNA-370-5P, and KLF7. Microarray analysis and qRT-PCR verified a circRNA termed circUBE2J2 that was downregulated in HCC. Kaplan–Meier survival analysis showed that downregulated circUBE2J2 was correlated with poorer survival. CircUBE2J2 expression in HCC cells was selectively regulated via luciferase reporter assays; circUBE2J2 and KLF7 were observed to directly bind to miR-370-5P. Furthermore, knockdown of circUBE2J2 in HCC could downregulate KLF7, the target of miR-370-5P, thus promoting the proliferation and migration of HCC cells. Then the related experiment suggested that circUBE2J2 could regulate the expression of KLF7 by sponging miR-370-5p. In summary, we infer that circUBE2J2 may act as a competing endogenous RNA (ceRNA) to regulate KLF7 expression through sponging miR-370-5P and play a regulatory functions in HCC. CircUBE2J2 may be a diagnostic biomarker and potential target for HCC therapy.Subject terms: Tumour biomarkers, Small RNAs     

Long intergenic noncoding RNA 00641 inhibits breast cancer cell proliferation,migration, and invasion by sponging miR-194-5p

Long noncoding RNAs have an essential role in the tumorigenesis of breast cancer (BC). Nonetheless, the consequences of long intergenic noncoding RNA 00641 (LINC00641) in BC remain unidentified. This study shows that LINC00641 expression level was decreased in BC tissues. LINC00641 expression level was negatively related to tumor size, lymph-node metastasis, as well as clinical stage. LINC00641 overexpression inhibited cell proliferation, migration, and invasion but stimulated apoptosis in BC cells. LINC00641 overexpression also remarkably reduced BC growth and metastasis in vivo. LINC00641 acts as a competitive endogenous RNA to sponge miR-194-5p. miR-194-5p level was higher in BC tissues and cells compared with normal-adjacent tissues and normal breast epithelial cell. miR-194-5p expression was negatively correlated with LINC00641 expression in BC tissues. miR-194-5p overexpression reversed the effects of LINC00641 on cell proliferation, cycle, apoptosis, migration, as well as invasion. In conclusion, LINC00641 inhibits BC cell proliferation, migration, as well as invasion by sponging miR-194-5p.     

Circular RNA circ_DROSHA alleviates the neural damage in a cell model of temporal lobe epilepsy through regulating miR-106b-5p/MEF2C axis

Temporal lobe epilepsy (TLE) is the most prevalent form of acquired epilepsy. Circular RNAs (circRNAs) have recently been highlighted as important regulators in TLE. Nevertheless, the role and mechanism of circRNA Drosha ribonuclease III (circ_DROSHA) in TLE pathogenesis are still unknown. Magnesium-free extracellular solution was used to establish the TLE cell model. The levels of circ_DROSHA, myocyte-specific enhancer factor 2C (MEF2C) and miR-106b-5p were determined by qRT-PCR and western blot. Cell proliferation was detected by the Cell Counting-8 Kit (CCK-8) assay, and cell apoptosis was measured by flow cytometry. Targeted relationships among circ_DROSHA, miR-106b-5p and MEF2C were confirmed by a dual-luciferase reporter or RNA immunoprecipitation (RIP) assay. Our data showed that circ_DROSHA was down-regulated in the serum samples of TLE patients and the TLE cell model. Circ_DROSHA up-regulation alleviated the cytotoxicity of the TLE cell model by enhancing cell proliferation and repressing cell apoptosis. Circ_DROSHA directly bound to miR-106b-5p. Moreover, miR-106b-5p represented a downstream effector of circ_DROSHA function. MEF2C was a direct target of miR-106b-5p, and miR-106b-5p knockdown relieved magnesium-free treatment-induced cell injury by up-regulating MEF2C. Furthermore, circ_DROSHA regulated MEF2C expression via sponging miR-106b-5p. Our study suggested that the enforced expression of circ_DROSHA alleviated the cell damage of the TLE cell model at least in part through the regulation of the miR-106b-5p/MEF2C axis.     

circEVI5 acts as a miR-4793-3p sponge to suppress the proliferation of gastric cancer

Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs (ncRNAs) with a covalently closed loop structure. Accumulating evidence shows that circRNAs play vital roles in the growth, metastasis, treatment and prognosis of various cancers. However, the detailed functions and underlying mechanisms of circEVI5 (hsa_circ_0013162) in gastric cancer (GC) remain undocumented. In this study, the expression levels and prognostic value of circEVI5 were validated in GC tissue samples by using qRT-PCR. circEVI5 was significantly downregulated in GC tissues and cells, and low circEVI5 expression was correlated with poor prognosis. Next, in vitro CCK-8 assay, EdU incorporation assay, PI staining cell cycle assay, and in vivo xenograft mouse models were conducted to assess the functions of circEVI5. Gain of function experiments indicated that circEVI5 could inhibit GC cell proliferation and retard the cell cycle. Moreover, bioinformatics prediction showed that circEVI5 binds to miR-4793-3p, while FOXO1 may be a target of miR-4793-3p. Pull-down assays, RNA immunoprecipitation (RIP) assays, luciferase assays, and western blot were used to confirm the interactions between circEVI5, miR-4793-3p, and FOXO1. Functional assays demonstrated that circEVI5 suppressed the proliferation of GC by sponging miR-4793-3p and increasing FOXO1 expression levels. In conclusion, our study demonstrated that circEVI5 can bind miR-4793-3p as a ceRNA to eliminate the negative regulation of FOXO1, therefore suppressing GC proliferation.Subject terms: Gastric cancer, Oncogenesis     

ADAR1 regulates ARHGAP26 gene expression through RNA editing by disrupting miR-30b-3p and miR-573 binding

Rho GTPase activating protein 26 (ARHGAP26) is a negative regulator of the Rho family that converts the small G proteins RhoA and Cdc42 to their inactive GDP-bound forms. It is essential for the CLIC/GEEC endocytic pathway, cell spreading, and muscle development. The present study shows that ARHGAP26 mRNA undergoes extensive A-to-I RNA editing in the 3′ UTR that is specifically catalyzed by ADAR1. Furthermore, the mRNA and protein levels of ARHGAP26 were decreased in cells in which ADAR1 was knocked down. Conversely, ADAR1 overexpression increased the abundance of ARHGAP26 mRNA and protein. In addition, we found that both miR-30b-3p and miR-573 target the ARHGAP26 gene and that RNA editing of ARHGAP26 mediated by ADAR1 abolished the repression of its expression by miR-30b-3p or miR-573. When ADAR1 was overexpressed, the reduced abundance of ARHGAP26 protein mediated by miR-30b-3p or miR-573 was rescued. Importantly, we also found that knocking down ADAR1 elevated RhoA activity, which was consistent with the reduced level of ARHGAP26. Conversely, when ADAR1 was overexpressed, the amount of RhoA-GTP decreased. The similar expression patterns of ARHGAP26 and ADAR1 in human tissue samples further confirmed our findings. Taken together, our results suggest that ADAR1 regulates the expression of ARHGAP26 through A-to-I RNA editing by disrupting the binding of miR-30b-3p and miR-573 within the 3′ UTR of ARHGAP26. This study provides a novel insight into the mechanism by which ADAR1 and its RNA editing function regulate microRNA-mediated modulation of target genes.     

Fibronectin-1 modulated by the long noncoding RNA OIP5-AS1/miR-200b-3p axis contributes to doxorubicin resistance of osteosarcoma cells

Chemoresistance has been an obstacle in the further improvement of 5-year survival rates of osteosarcoma (OS) patients, but the underlying mechanism of chemo-resistance remains unclear. A comprehensive analysis of mRNAs and noncoding RNAs related to OS chemo-resistance could help solve this problem. In the current study, we first identified that fibronectin-1 (FN1), screened by microarray analysis in three paired chemo-resistant and chemo-sensitive OS cell lines, was significantly upregulated in the chemo-resistant OS cell lines and tissues and was related to unfavourable prognosis. Further functional assays revealed that FN1 inhibition greatly increased the sensitivity of OS cells to doxorubicin in vitro and in vivo, whereas FN1 overexpression had the opposite effect. Moreover, mechanistic investigation demonstrated, by a series of assays that included luciferase reporter gene, RNA immunoprecipitation, RNA pull-down and rescue assays, that FN1 expression was regulated by the oncogenic long noncoding RNA (lncRNA) OIP5-AS1 through sponging miR-200b-3p. Thus, these results indicated the role and potential application of the lncRNA OIP5-AS1/miR-200b-3p/FN1 regulatory pathway as a promising target in treatment of OS chemo-resistance.     

LINC00958 facilitates cervical cancer cell proliferation and metastasis by sponging miR-625-5p to upregulate LRRC8E expression

Accepted as a malignant tumor worldwide, cervical cancer (CC) has attracted much attention for its high incidence and mortality rates. Previous studies have elucidated the critical regulatory function that long noncoding RNAs (lncRNAs) exert on the tumorigenesis and progression of diverse tumors. Although multiple investigations have depicted that LINC00958 has a great impact on the complex biological process of many cancers, knowledge concerning the regulatory role of LINC00958 in CC remains limited and needs to be further explored. In our study, LINC00958 expression was evidently overexpressed in CC tissues and cells. Besides this, LINC00958 negatively regulated miR-625-5p expression and was verified to bind with miR-625-5p in CC. Subsequently, it was testified by a series of experiments that LINC00958 promotes CC cell proliferation and metastasis by sponging miR-625-5p. Furthermore, the leucine-rich repeat containing the eight family member E (LRRC8E) could bind with miR-625-5p, and its expression was negatively modulated by miR-625-5p, whereas positively regulated by LINC00958 in CC. Final rescue assays verified the effects of LINC0095/LRRC8E interaction and miR-625-5p/LRRC8E interaction on CC cell proliferation and metastasis. Collectively, LINC00958 facilitates CC cell proliferation and metastasis via the miR-625-5p/LRRC8E axis.     

Downregulation of circDYNC1H1 exhibits inhibitor effect on cell proliferation and migration in hepatocellular carcinoma through miR-140-5p

Circular RNAs have been found to be aberrantly expressed in tumors and their significance in tumorigenesis has been focused on. The role of circDYNC1H1 in hepatocellular carcinoma (HCC) pathogenesis and its relationship with miR-140-5p were explored. The expression of circDYNC1H1, miR-140-5p, and SULT2B1 in HCC tissues and cells was measured, and Pearson's analysis was used to analyze their expression correlation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays were performed to determine cell proliferation and migration. Binding between circDYNC1H1 and miR-140-5p was evaluated with RNA pull-down assay. A luciferase reporter assay was conducted to assess the interaction between circDYNC1H1 and miR-140-5p and between miR-140-5p and SULT2B1. circDYNC1H1 was highly expressed in HCC tissues (n = 20), and it was negatively associated with the expression of miR-140-5p but positively correlated with SULT2B1 messenger RNA expression. circDYNC1H1 was upregulated in cell lines of HCC. Interference of circDYNC1H1 suppressed cell proliferation and migration of HCC. circDYNC1H1 acted as a sponge of miR-140-5p. miR-140-5p controlled SULT2B1 expression by targeting its 3′-untranslated region. circDYNC1H1 enhanced SULT2B1 expression via sponging miR-140-5p. Downregulation of circDYNC1H1 disturbed cell proliferation and migration of HCC through miR-140-5p/SULT2B1 pathway. Silencing of circDYNC1H1 delayed tumor growth in HCC mouse model. Acting like a sponge of miR-140-5p, silenced circDYNC1H1 downregulated SULT2B1 to restrain HCC cell proliferation and migration, which is adverse to HCC growth and progression.     

Long noncoding RNA AC073284.4 suppresses epithelial–mesenchymal transition by sponging miR-18b-5p in paclitaxel-resistant breast cancer cells

Breast cancer (BC) is the most prevalent malignant cancer in the world, is the leading cause of cancer-related death female. Recently, there is accumulating evidence that long noncoding RNAs (lncRNAs) might as an important role in the progression of BC. (epithelial-mesenchymal transition (EMT) is considered to play a vital role in tumor cells migration and invasion. Nevertheless, the entire biological mechanisms and functions of lncRNAs in tumor migration, invasion, and EMT remain uncertain. In the present research, we observed that the expression of lncRNA AC073284.4 was downregulated in BC paclitaxel-resistant (PR) cells (MCF-7/PR) and tissues. Bioinformatics analysis predicted that miR-18b-5p was a direct target of AC073284.4, which has been validated by dual-luciferase reporter gene assay. We further proved that AC073284.4 could directly bind to miR-18b-5p and relieve the suppression for dedicator of cytokinesis protein 4 (DOCK4). Furthermore, the underlying functional experiments demonstrated that AC073284.4 might sponge miR-18b-5p to attenuate the invasion, metastasis, and EMT of BC cell through upregulating DOCK4 expression. In summary, AC073284.4 might serve as a competing endogenous RNA (ceRNA) in BC progression via modulating miR-18b-5p/DOCK4 axis, which weakens EMT and migration of BC. These results suggesting that AC073284.4 might function as a potential novel diagnostic biomarker in the progression of BC.     

Cucurbitacin B suppresses proliferation of pancreatic cancer cells by ceRNA: Effect of miR-146b-5p and lncRNA-AFAP1-AS1

Cucurbitacin B (CuB) is a natural tetracyclic triterpene product that displays antitumor activity against a wide variety of cancers. In this study, we explored the antipancreatic cancer activity of CuB via the inhibition of expression of the cancer-related long noncoding RNA, actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1). CuB arrested pancreatic cancer (PC) cells in the G2/M cell cycle phase by suppressing the expression of AFAP1-AS1. Insights into the mechanisms of competing endogenous RNAs (ceRNAs) gained from bioinformatics analysis and luciferase activity assays showed that the epidermal growth factor receptor (EGFR) and AFAP1-AS1 directly compete for miR-146b-5p binding. CuB-induced high miR-146b-5p expression and inhibited the expression of AFAP1-AS1. In summary, reducing the expression of endogenous AFAP1-AS1 effectively increased the available concentration of miR-146b-5p in PC, whereas miR-146b-5p overexpression prevented the expression of endogenous AFAP1-AS1. In particular, we hypothesized that AFAP1-AS1 might act as a ceRNA, effectively becoming a sponge for miR-146b-5p, thereby activating the expression of the EGFR. Thus, CuB suppresses the proliferation, in vitro and in vivo, of PC cells through the ceRNA effect of AFAP1-AS1 on miR-146b-5p.     

CircCCNB1 silencing acting as a miR-106b-5p sponge inhibited GPM6A expression to promote HCC progression by enhancing DYNC1I1 expression and activating the AKT/ERK signaling pathway

Background: Circular RNAs (circRNAs), which generally act as microRNA (miRNA) sponges to competitively regulate the downstream target genes of miRNA, play an essential role in cancer biology. However, few studies have been reported on the role of circRNA based competitive endogenous RNA (ceRNA) network in hepatocellular carcinoma (HCC). Herein, we aimed to screen and establish the circRNA/miRNA/mRNA networks related to the prognosis and progression of HCC and further explore the underlying mechanisms of tumorigenesis.Methods: GEO datasets {"type":"entrez-geo","attrs":{"text":"GSE97332","term_id":"97332"}}GSE97332, {"type":"entrez-geo","attrs":{"text":"GSE108724","term_id":"108724"}}GSE108724, and {"type":"entrez-geo","attrs":{"text":"GSE101728","term_id":"101728"}}GSE101728 were utilized to screen the differentially expressed circRNAs (DE-circRNAs), DE-miRNAs, and DEmRNAs between HCC and matched para-carcinoma tissues. After six RNA-RNA predictions and five intersections between DE-RNAs and predicted RNAs, the survival-related RNAs were screened by the ENCORI analysis tool. The ceRNA networks were constructed using Cytoscape software, based on two models of up-regulated circRNA/down-regulated miRNA/up-regulated mRNA and down-regulated circRNA/up-regulated miRNA/down-regulated mRNA. The qRT-PCR assay was utilized for detecting the RNA expression levels in HCC cells and tissues. The apoptosis, Edu, wound healing, and transwell assays were performed to evaluate the effect of miR-106b-5p productions on the proliferation, invasion, and metastasis of HCC cells. In addition, the clone formation, cell cycle, and nude mice xenograft tumor assays were used to investigate the influence of hsa_circ_0001495 (circCCNB1) silencing and overexpression on the proliferation of HCC cells in vitro and in vivo. Furthermore, the mechanism of downstream gene DYNC1I1 and AKT/ERK signaling pathway via the circCCNB1/miR-106b-5p/GPM6A network in regulating the cell cycle was also explored.Results: Twenty DE-circRNAs with a genomic length less than 2000bp, 11 survival-related DE-miRNAs, and 61 survival-related DE-mRNAs were screened out and used to construct five HCC related ceRNA networks. Then, the circCCNB1/miR-106b-5p/GPM6A network was randomly selected for subsequent experimental verification and mechanism exploration at in vitro and in vivo levels. The expression of circCCNB1 and GPM6A were significantly down-regulated in HCC cells and cancer tissues, while miR-106b-5p expression was up-regulated. After transfections, miR-106b-5p mimics notably enhanced the proliferation, invasion, and metastasis of HCC cells, while the opposite was seen with miR-105b-5p inhibitor. In addition, circCCNB1 silencing promoted the clone formation ability, the cell cycle G1-S transition, and the growth of xenograft tumors of HCC cells via GPM6A downregulation. Subsequently, under-expression of GPM6A increased DYNC1I1 expression and activated the phosphorylation of the AKT/ERK pathway to regulate the HCC cell cycle.Conclusions: We demonstrated that circCCNB1 silencing promoted cell proliferation and metastasis of HCC cells by weakening sponging of oncogenic miR-106b-5p to induce GPM6A underexpression. DYNC1I1 gene expression was up-regulated and further led to activation of the AKT/ERK signaling pathway.     

Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis

miRNAs have emerged as crucial regulators in the regulation of development as well as human diseases, especially tumorigenesis. The aims of this study are to evaluate miR-30b-5p expression pattern and mechanism in gastric carcinogenesis due to which remains to be determined. Expression of miR-30b-5p was analyzed in 51 gastric cancer cases and 4 cell lines by qRT-PCR. The effect of DNA methylation on miR-30b-5p expression was assessed by MSP and BGS. In order to know whether DNMT1 increased miR-30b-5p promoter methylation, DNMT1 was depleted in cell lines AGS and BGC-823. The role of miR-30b-5p on cell migration was evaluated by wound healing assays. Decreased expression of miR-30b-5p was found in gastric cancer samples. In tumor, the expression level of miR-30b-5p was profound correlated with lymph node metastasis (P = 0.019). The level of miR-30b-5p may be restored by DNA demethylation and DNMT1 induced miR-30b-5p promoter methylation. In vitro functional assays implied that enforced miR-30b-5p expression affected cell migration, consistent with tissues analysis. Our findings uncovered that miR-30b-5p is significantly diminished in gastric cancer tissues, providing the first insight into the epigenetic mechanism of miR-30b-5p down-regulation, induced by DNMT1, and the role of miR-30b-5p in gastric cancer carcinogenesis. Overexpression of miR-30b-5p inhibited cell migration. Thus, miR-30b-5p may represent a potential therapeutic target for gastric cancer therapy.     

LINC00152 promotes cell cycle progression in hepatocellular carcinoma via miR-193a/b-3p/CCND1 axis

Long intergenic non-coding RNA 00152 (LINC00152) is aberrantly expressed in various human malignancies and plays an important role in the pathogenesis. Here, we found that LINC00152 is upregulated in hepatocellular carcinoma (HCC) tissues as compared to adjacent non-neoplastic tissues; gain-and-loss-of-function analyses in vitro showed that LINC00152 facilitates HCC cell cycle progression through regulating the expression of CCND1. LINC00152 knockdown inhibits tumorigenesis in vivo. MS2-RIP analysis indicated that LINC00152 binds directly to miR-193a/b-3p, as confirmed by luciferase reporter assays. Furthermore, ectopic expression of LINC00152 partially halted the decrease in CCND1 expression and cell proliferation capacity induced by miR-193a/b-3p overexpression. Thus, LINC00152 acts as a competing endogenous RNA (ceRNA) by sponging miR-193a/b-3p to modulate its target gene, CCND1. Our findings establish a ceRNA mechanism regulating cell proliferation in HCC via the LINC00152/miR-193a/b-3p/CCND1 signalling axis, and identify LINC00152 as a potential therapeutic target for HCC.     

LncRNA SOX2-OT regulates proliferation and metastasis of nasopharyngeal carcinoma cells through miR-146b-5p/HNRNPA2B1 pathway

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with a high mortality on account of its frequent metastasis and poor prognosis. An extensive body of investigations has proven that long noncoding RNAs are implicated in a variety of biological processes. Although SOX2-OT has been reported to play an oncogenic role in osteosarcoma, the mechanism of SOX2-OT-driven NPC progression is still obscure. The aim of this study was to elucidate the biological function of SOX2-OT and the related possible mechanism in NPC. In our study, SOX2-OT was notably elevated in NPC samples and cells. Further, a high expression level of SOX2-OT was correlated with poor clinical outcomes of NPC. Results from loss-of-function experiments suggested that knockdown of SOX2-OT repressed cell proliferation, arrested cell cycle, facilitated cell apoptosis, and inhibited cell metastasis of NPC. To further investigate the molecular mechanism of SOX2-OT, miR-146b-5p was found to directly bind to SOX2-OT, which mediated the role of SOX2-OT in NPC tumorigenesis. In addition, HNRNPA2B1 was a target of miR-146b-5p and SOX2-OT modulated the expression of HNRNPA2B1 through competitively binding to miR-146b-5p. At last, we discovered that SOX2-OT regulated NPC progression by targeting miR-146b-5p/HNRNPA2B1 pathway, which may provide more innovative targets for the treatment of patients with NPC.     

circUBE3C modulates myoblast development by binding to miR-191 and upregulating the expression of p27

Noncoding RNAs, including miRNAs (microRNAs) and circRNAs (circular RNA), are crucial regulators of myoblast proliferation and differentiation during muscle development. However, the specific roles and molecular mechanisms of circRNAs in muscle development remain poorly understood. Based on the existing circRNA-miRNA-mRNA network, our study focuses on circUBE3C, exploring its differential expression in fetal and adult muscle tissue of the cattle and investigating its impact on myoblast proliferation, apoptosis, and differentiation. The functional analysis of overexpression plasmids and siRNAs (small interfering RNAs) targeting circUBE3C was comprehensively evaluated by employing an array of advanced assays, encompassing CCK-8 (cell counting kit-8), EdU (5-ethynyl-20-deoxyuridine), flow cytometry, western blot analysis, and RT-qPCR. In vivo investigations indicated that overexpression of circUBE3C impedes the process of skeletal muscle regeneration. Mechanistically, we demonstrated that circUBE3C interacts with miR-191 and alleviates the suppression of p27 through cytoplasmic separation, bioinformatics prediction, dual-luciferase reporter assay, and RIP (RNA immunoprecipitation). Our findings indicate that the novel circRNA circUBE3C competitively binds to miR-191, thereby inhibiting proliferation and promoting apoptosis in bovine primary myoblasts and unveiling a regulatory pathway in bovine skeletal muscle development. These findings expand our understanding of circRNA functions in mammals and provide a basis for further exploration of their role in myogenesis and muscle diseases.     

Circ_0061012 contributes to IL-22-induced proliferation,migration and invasion in keratinocytes through miR-194-5p/GAB1 axis in psoriasis

Psoriasis is a chronic inflammation-associated skin disorder featured by excessive proliferation and abnormal differentiation of keratinocytes. Here, we intended to investigate the role of circular RNA 0061012 (circ_0061012) in psoriasis progression. The expression of circ_0061012, SLMO2-ATP5E readthrough (SLMO2-ATP5E) messenger RNA (mRNA), microRNA-194-5p (miR-194-5p) and GRB2 associated binding protein 1 (GAB1) mRNA was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and metastasis were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Western blot assay was used to measure the protein levels of Ki67, matrix metallopeptidase 9 (MMP9) and GAB1. Dual-luciferase reporter assay and RNA immune co-precipitation (RIP) assay were used to verify the interaction between miR-194-5p and circ_0061012 or GAB1. Circ_0061012 abundance was significantly enhanced in lesional skin samples from psoriasis patients than that in normal skin specimens from healthy volunteers. Interleukin-22 (IL-22) treatment increased the expression of circ_0061012 in a dose-dependent manner. Circ_0061012 silencing alleviated IL-22-induced promoting effects in the proliferation, migration and invasion of HaCaT cells. Circ_0061012 interacted with miR-194-5p, and miR-194-5p knockdown counteracted circ_0061012 silencing-mediated influences in IL-22-induced HaCaT cells. GAB1 was a target of miR-194-5p in HaCaT cells, and miR-194-5p hampered proliferation and metastasis which were induced by IL-22 partly through targeting GAB1. Circ_0061012 elevated the expression of GAB1 through sponging miR-194-5p in HaCaT cells. Circ_0061012 accelerated IL-22-induced proliferation and metastasis in HaCaT cells through enhancing GAB1 expression via sponging miR-194-5p in psoriasis.