Knockdown of circRAD23B Exerts Antitumor Response in Colorectal Cancer via the Regulation of miR-1205/TRIM44 axis.

BACKGROUND: Colorectal cancer (CRC) is a common cancer with high metastatic property. Circular RNAs (circRNAs) have important involvement in cancer processes. This study focused on the regulation of circRNA RAD23 homologue B (circRAD23B) in CRC. METHODS: The levels of circRAD23B, microRNA-1205 (miR-1205), and tripartite motif-44 (TRIM44) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Functional analyses were performed by Cell Counting Kit-8 (CCK-8) for cell proliferation, flow cytometry for cell cycle or cell apoptosis, and transwell assay for cell migration and invasion. Western blot was administrated for protein detection. The interaction of targets was analyzed by dual-luciferase reporter and RNA pull-down assays. The in vivo experiment was conducted via xenograft tumor in mice. RESULTS: We identified that circRAD23B was overexpressed in CRC tissues and cells. CRC cell proliferation, cell cycle progression, and cell metastasis were inhibited, while apoptosis was promoted by downregulating circRAD23B. Target analysis indicated that circRAD23B-targeted miR-1205 and TRIM44 were downstream genes of miR-1205. Moreover, the antitumor response of circRAD23B downregulation and miR-1205 overexpression was, respectively, achieved by increasing miR-1205 and decreasing TRIM44. CircRAD23B could regulate TRIM44 level by sponging miR-1205. In vivo, circRAD23B knockdown also reduced CRC tumorigenesis via the miR-1205/TRIM44 axis. CONCLUSION: These results suggested that the inhibition of circRAD23B retarded the progression of CRC via acting on the miR-1205/TRIM44 axis. CircRAD23B might be a novel target in CRC treatment.

miR-1205/DNAJB1 reverses docetaxel chemoresistance in human triple negative breast carcinoma cells via regulation of mutp53/TAp63 signaling.

Chemoresistance is the major cause of therapeutic failure in human triple negative breast carcinoma (TNBC). Docetaxel (DOC), a first-line therapeutic drug in TNBC treatment, is limited for long-term use due to the development of chemoresistance. Thus, overcoming chemoresistance of DOC remains an important challenge to improve patient's outcome of TNBC. In this study, we aimed to investigate the molecular mechanism behind DOC chemoresistance and the possible therapeutic effects of miRNAs. Utilizing qRT-PCR analysis, we discovered that miR-1205 is gradually downregulated in human triple negative breast carcinoma MDA-MB-231 and docetaxel-resistant MDA-MB-231 (MDA-MB-231/DOC) cells compared with Hs 578Bst normal human breast fibroblasts. Cell viability, cell cycle and apoptosis assays in MDA-MB-231/DOC cells indicated that miR-1205 overexpression enhances docetaxel sensitivity by reducing cell viability as well as inducing G2/M cell cycle arrest and cell apoptosis. Western blot analysis, dual-luciferase reporter assay, co-immunoprecipitation assay and chromatin immunoprecipitation assay revealed that miR-1205 overexpression disrupts the stable complex formation of DNAJB1, mutp53 and TAp63 by directly reducing DNAJB1 expression, which abates the sequestrating effect of mutp53 on TAp63, thereby leading to the enhanced DOC sensitivity in MDA-MB-231/DOC cells. Our findings demonstrate the role of the miR-1205/DNAJB1 axis in the docetaxel resistance of TNBC, which may offer a promising therapeutic approach to resolve docetaxel resistance in TNBC.

Circ_0082182 promotes oncogenesis and metastasis of colorectal cancer in vitro and in vivo by sponging miR-411 and miR-1205 to activate the Wnt/ß-catenin pathway.

BACKGROUND: Circular RNAs (circRNAs) are a class of endogenous single-strand RNA transcripts with crucial regulation in human cancers. The objective of this study is to investigate the role of circ_0082182 in CRC and its specific functional mechanism. METHODS: The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the levels of circ_0082182, microRNA-411 (miR-411) and microRNA-1205 (miR-1205). Cell proliferation was detected by Cell counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used for determining cell cycle and cell apoptosis. Cell apoptosis was also assessed by caspase3 and caspase9 activities. Cell migration and invasion were examined using scratch assay and transwell assay. The interaction between circ_0082182 and miRNA was validated by the dual-luciferase reporter and biotinylated RNA pull-down assays. Wnt/ß-catenin pathway and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by Western blot. Xenograft model was established for the research of circ_0082182 in vivo. RESULTS: Circ_0082182 was upregulated in CRC and could predict the poor prognosis of CRC patients. Functionally, circ_0082182 promoted CRC cell proliferation, cell cycle progression, and metastasis while inhibited apoptosis. Subsequently, circ_0082182 was shown to act as the sponges of miR-411 and miR-1205. MiR-411 and miR-1205 were identified as tumor inhibitors in CRC. Furthermore, circ_0082182 promoted the CRC progression via sponging miR-411 and miR-1205. Moreover, circ_0082182 facilitated the Wnt/ß-catenin pathway and EMT process by targeting miR-411 and miR-1205. In vivo, circ_0082182 accelerated the CRC tumorigenesis and EMT process by activating the Wnt/ß-catenin pathway by downregulating the expression of miR-411 or miR-1205. CONCLUSION: This study showed that circ_0082182 functioned as an oncogene in the developing process of CRC by sponging miR-411 or miR-1205 to activate the Wnt/ß-catenin pathway. Circ_0082182 might be a molecular target in the diagnosis and treatment of CRC.

CircASXL1 knockdown represses the progression of colorectal cancer by downregulating GRIK3 expression by sponging miR-1205.

BACKGROUND: Colorectal cancer (CRC) is a common aggressive tumor that poses a heavy burden to human health. An increasing number of studies have reported that circular RNA (circRNA) is involved in the progression of CRC. In this study, the special profiles of circASXL1 (circ_0001136) in CRC progression were revealed. METHODS: The expression of circASXL1, microRNA-1205 (miR-1205), and glutamate ionotropic receptor kainate type subunit 3 (GRIK3) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression was determined by Western blot or immunohistochemistry. Cell colony-forming ability was investigated by colony formation assay. Cell cycle and apoptosis were demonstrated using cell-cycle and cell-apoptosis analysis assays, respectively. Cell migration and invasion were detected by wound-healing and transwell migration and invasion assays, respectively. The binding sites between miR-1205 and circASXL1 or GRIK3 were predicted by circBank or miRDB online database, and identified by dual-luciferase reporter assay. The impact of circASXL1 on tumor formation in vivo was investigated by in vivo tumor formation assay. RESULTS: CircASXL1 and GRIK3 expression were apparently upregulated, and miR-1205 expression was downregulated in CRC tissues and cells relative to control groups. CircASXL1 knockdown inhibited cell colony-forming ability, migration and invasion, whereas induced cell arrest at G0/G1 phase and cell apoptosis in CRC cells; however, these effects were attenuated by miR-1205 inhibitor. Additionally, circASXL1 acted as a sponge for miR-1205, and miR-1205 was associated with GRIK3. Furthermore, circASXL1 silencing hindered tumor formation by upregulating miR-1205 and downregulating GRIK3 expression. CONCLUSION: CircASXL1 acted an oncogenic role in CRC malignant progression via inducing GRIK3 through sponging miR-1205. Our findings provide a theoretical basis for studying circASXL1-directed therapy for CRC.

Hsa_circ_0039411 promotes tumorigenesis and progression of papillary thyroid cancer by miR-1179/ABCA9 and miR-1205/MTA1 signaling pathways.

Papillary thyroid cancer (PTC) is a common malignancy in endocrine system worldwide. Increasing evidence has shown that dysregulation of circular RNAs (circRNAs) could contribute to PTC tumorigenesis. The aims of this project are to investigate the potential role and molecular mechanism of hsa_circ_0039411 in PTC. In the project, RT-qPCR was performed to measure the expression profile of hsa_circ_0039411 in PTC tissues and cells. Cell counting kit-8, clonogenic, flow cytometric, and transwell experiments were used to identify the biological role of hsa_circ_0039411 on PTC cell progression. Bioinformatics methods, along with the dual-luciferase reporter test, was used to identify the potential mechanism of hsa_circ_0039411. Hsa_circ_0039411 was identified as enhanced in PTC tissues/cells. Gain-of-function experiments indicated that hsa_circ_0039411 facilitated PTC cell growth, migration, and invasion and inhibited cell apoptosis. Knockdown of hsa_circ_0039411 caused the opposite effects mentioned above. The mechanism exploration showed that hsa_circ_0039411 functioned as a sponge for miR-1179 and miR-1205 to elevate ATP-binding cassette transporter A9 (ABCA9) and metastasis-associated 1 (MTA1) expression at the post-transcriptional level, respectively. Further investigation confirmed that the functions of hsa_circ_0039411 are dependent on its modulation of ABCA9 and MTA1 in PTC cells. This study uncovered a mechanism of hsa_circ_0039411 in PTC, which might act as a novel therapeutic target for PTC.

Circular RNA circMAN2B2 facilitates glioma progression by regulating the miR-1205/S100A8 axis.

The aim of this study was to research the mechanism of circMAN2B2 in the development of glioma. In our study, we found that circMAN2B2 has a higher expression in glioma tissues and cells, which was negatively related to the overall survival of glioma patients. The cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine labeling assay, transwell assay, and the nude mice assay indicated that knockdown of circMAN2B2 inhibited the cell proliferation, invasion, migration and decreased tumor size. In terms of mechanism, knockdown of circMAN2B2 increased the expression of miR-1205. Moreover, circMAN2B2 regulated S100A8 expression by inhibiting miR-1205. We also showed that knockdown of S100A8 inhibited cell proliferation, invasion, and migration. Increasing S100A8 expression rescued the effect of si-circMAN2B2. In conclusion, circMAN2B2 could improve cell proliferation, invasion, and migration of the glioma by inhibiting miR-1205 and promoting the expression of S100A8.

Elevation of circular RNA circ-POSTN facilitates cell growth and invasion by sponging miR-1205 in glioma.

Glioma is the most common type of primary intracranial tumor. Dysregulation of circular RNAs (circRNAs) plays a critical role in multiple solid tumors. However, the expression profiles of circRNAs and their functions in glioma have been rarely studied. The current work aims to investigate the clinical significance of a novel circRNA, circ-POSTN, in glioma and explore its biological functions and mechanisms in the progression of glioma. We found that circ-POSTN was highly expressed in glioma tissue samples and cells. High circ-POSTN expression was significantly linked to larger tumor size, higher World Health Organization grades, and shorter overall survival. Furthermore, silencing of circ-POSTN in glioma cells could decrease cell growth, migratory and invasive potential, and induce cell apoptosis in LN229 cells. On the contrary, ectopically expressed circ-POSTN induced the opposite effects in the U251 cell line. By bioinformatic prediction and luciferase reporter assay, we identified that miR-1205 could be sponged by circ-POSTN. Further rescue assays demonstrated that the oncogenic functions of circ-POSTN are partly attributed to its regulation of miR-1205 in glioma cells. Taken together, our data suggest that circ-POSTN plays an oncogenic role in glioma progression and may serve as a novel therapeutic target in this deadly disease.

Upregulation of circular RNA circ_0034642 indicates unfavorable prognosis in glioma and facilitates cell proliferation and invasion via the miR-1205/BATF3 axis.

Accumulating studies demonstrate the critical role of circular RNAs (circRNAs) in the pathogenesis of various types of cancers. Previously, hsa_circ_0034642 has been found elevated in glioma tissues compared with the normal tissues, as proved by high-throughput microarray. We further investigated its expression level in 52 paired tissues and different glioma cell lines by quantitative reverse transcription-polymerase chain reaction. In addition, Fisher's exact test, Kaplan-Meier curves, and Cox analyses were performed to elucidate the clinical significance of hsa_circ_0034642. For the part of functional assays, gain/loss-of-function assays were conducted to measure cell growth, apoptosis, and metastatic properties affected by hsa_circ_0034642. Furthermore, the mechanisms of hsa_circ_0034642 were investigated by dual-luciferase reporter assays. As the results demonstrated, hsa_circ_0034642 was boosted in glioma tissues and cells. Overexpression of hsa_circ_0034642 was associated with clinical severity and poor prognosis. What is more, elevated hsa_circ_0034642 strikingly facilitated cell proliferation, migratory and invasive capacities, and decreased apoptotic cells. Mechanistically, hsa_circ_0034642 sponges miR-1205. miR-1205 regulates BATF3 level through targeting its 3'-untranslated region. In summary, hsa_circ_0034642 might play a key role in this malignancy.

Circular RNA circ_0034642 elevates BATF3 expression and promotes cell proliferation and invasion through miR-1205 in glioma.

Growing evidence indicates that circular RNA (circRNA) plays an important role in the regulation of tumor biological behaviors. In this study, we aimed to explore the role of a novel circRNA, circ_0034642, in glioma. qRT-PCR was conducted to evaluate the levels of circ_0034642 in glioma tissues and cells. In addition, the clinical severity and prognostic role of circ_0034642 were illustrated. Functionally, loss and gain-of function assays were performed by CCK-8, colony-forming, flow cytometric and transwell experiments in glioma cells. Moreover, luciferase reporter assay was used to detect the mechanism of circ_0034642. Circ_0034642 was upregulated in glioma tissues and cell lines. Overexpressed circ_0034642 was correlated with adverse phenotypes in the patients with glioma. In addition, circ_0034642 could be regarded as a prognostic predictor for glioma patients. Moreover, circ_0034642 could promote cell proliferation, migratory and invasive capacities and inhibit cell apoptosis. For the mechanism investigation, circ_0034642 was proved to be a sponge of miR-1205, and miR-1205 could regulate BATF3 expression via targeting 3'UTR of BATF3. Rescue assays also illustrated that the oncogenic function of circ_0034642 is partly attributed to its modulation on miR-1205/BATF3 axis. Collectively, circ_0034642/miR-1205/BATF3 pathway may play an important role in glioma.

Overexpressing circular RNA hsa_circ_0002052 impairs osteosarcoma progression via inhibiting Wnt/ß-catenin pathway by regulating miR-1205/APC2 axis.

Circular RNAs (circRNAs) are a novel class of noncoding RNAs, whose importance in cancer has been gradually acknowledged. However, the functions of circRNAs in tumorigenesis have not been fully understood. In the present study, we identified a novel circRNA hsa_circ_0002052 significantly downregulated in osteosarcoma (OS) tissues and cell lines. Moreover, we found that hsa_circ_0002052 could act as a biomarker to indicate the prognosis of OS patients. Functionally, we showed that hsa_circ_0002052 overexpression significantly suppressed OS cell proliferation, migration and invasion while promoting apoptosis in vitro. Similarly, in vivo assay indicated that ectopic expression of hsa_circ_0002052 impaired OS cell growth. In terms of mechanism, we found that hsa_circ_0002052 inhibited miR-1205 while miR1205 targeted APC2, a negative regulator of Wnt/ß-catenin signaling pathway. By releasing the inhibition of miR-1205 on APC2 expression, hsa_circ_0002052 suppressed the activation of Wnt/ß-catenin signaling pathway, leading to attenuated OS progression. Taken together, our study for the first time revealed a suppressive circRNA hsa_circ_0002052 involved in OS progression. Our study suggested hsa_circ_0002052/miR-1205/APC2/Wnt/ß-catenin axis might be a potential target for OS therapy.

MicroRNA-1205 promotes breast cancer cell metastasis by regulating epithelial-to-mesenchymal transition via targeting of CDK3.

Metastasis poses a huge obstacle to the survival of breast cancer patients. The microRNA miR-1205 acts as a tumor suppressor in various cancers, but its roles in breast cancer and metastasis remain unclear. To elucidate its function in breast cancer progression, we analyzed miR-1205 expression in human tumor samples and carried out a series of functional studies in in vitro and in vivo. miR-1205 was expressed more highly in metastatic breast tumor samples than in non-metastatic samples and was associated with lymph node metastasis, clinical stage, and poor prognosis. Moreover, miR-1205 promoted breast cancer cell invasiveness in vitro and metastasis in mice by directly targeting CDK3 and reducing CDK3 protein levels. We also showed that CDK3 interacts with Snail protein, inducing Snail degradation via the ubiquitin-proteasome system and potentially affecting epithelial-to-mesenchymal transition. Furthermore, analysis of clinical tissue samples indicated that CDK3 and miR-1205 levels were inversely correlated in lymph node metastasis-positive primary tumors. This study demonstrated the pro-metastatic role of miR-1205 in breast cancer, mediated via a novel miR-1205/CDK3/Snail axis. Moreover, we identified miR-1205 and CDK3 as potential markers of invasion and progression in breast cancer.

CircMYBL2 facilitates hepatocellular carcinoma progression by regulating E2F1 expression.

Circular RNAs (circRNAs) have been recognized as pivotal regulators in tumorigenesis, yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma (HCC) remain elusive. We sought to unveil the expression profile and biological role of circMYBL2 in HCC. Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells, and qRT‒PCR analysis was then performed in HCC cell lines and tissues, revealing significant upregulation of circMYBL2. Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression. Furthermore, bioinformatics analysis, qRT‒PCR analysis, luciferase reporter assays, and western blot analysis were employed to investigate the interplay among circMYBL2, miR-1205, and E2F1. CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines. Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells, whereas circMYBL2 knockdown elicited contrasting effects. Mechanistically, our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205. Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis, suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.

Circular RNA circIL21R promotes cervical cancer cells proliferation and migration by sponging the miR-1205/PTBP1 axis.

Increasing research has shown that the abnormal expression of circRNAs is closely related to tumorigenesis, apoptosis, and patient prognosis in cervical cancer. This study aimed to reveal the procancer role of circIL21R in cervical cancer and investigate its related molecular mechanisms. Bioinformatics analysis revealed that circIL21R promotes the progression of cervical cancer via the miR-1205/PTBP1 axis. CircIL21R expression was significantly greater in tumor tissue than in adjacent normal tissue, and higher circIL21R expression indicated shorter survival. We applied MTS assays, EdU assays, and Transwell assays to show that the overexpression of circIL21R promoted cervical cancer cell proliferation and invasion. Mechanistically, circIL21R promoted the expression of PTBP1 by sponging miR-1205. Moreover, rescue assays confirmed that regulating the expression of miR-1205 or PTBP1 could reverse the tumorigenic effect caused by circIL21R overexpression. In addition, circIL21R promoted the tumorigenesis of cervical cancer in vivo. In summary, our study demonstrated that circIL21R was highly expressed in cervical cancer and upregulated PTBP1 expression by acting as a ceRNA for miR-1205, making outstanding contributions to several malignant biological processes in cervical cancers, such as growth, proliferation, and invasion. CircIL21R is a potential biomarker for the diagnosis and treatment of cervical cancer.

Downregulation of circular RNA ETS1 promotes SLE activity and inhibits Treg cell differentiation through miR-1205/FoxP3 molecular axis.

PURPOSE: This study aimed to explore the mechanism by which systemic lupus erythematosus (SLE) activity is promoted through Treg inhibition from the perspective of ceRNA. METHODS: qRT-PCR was used to detect the expressions of circETS1, miR-1205, and FoxP3 in clinical SLE patient samples. Overexpression of circETS1and miR-1205, along with knockdown of miR-1205 and FoxP3 were conducted in CD4+ T cells, while the proliferation of helper T cell 17 (Th17) and regulatory T cell (Treg) was detected. Arescue assay was performed to verify the molecular mechanism of circETS1/miR-1205/Foxp3 mRNA axis in regulating CD4+ T cell differentiation. In the in vivo experiment, the expression of miR-1205 in SLE mice was intervened, and renal function, inflammatory factors, and serum complement were measured. Additionally, Treg/Th17 cell ratio was detected by flow cytometry. RESULTS: In SLE patients, Treg cells were found to decrease, while Th17 cells increased. Transfection with circETS1 overexpression led to CD4+ T cells differentiating into Treg cells, causing an imbalance in the Th17/Treg ratio. Transfection of miR-1205 mimic and si-FoxP3 could reverse the effect of circETS1 overexpression. Moreover, inhibiting the expression of miR-1205 showed therapeutic effects on SLE mice. CONCLUSION: circETS1 inhibits Treg via the miR-1205/FoxP3 axis, thereby promoting SLE activity, which may become a new target for SLE treatment.

Circ_0001982 Up-regulates the Expression of E2F1 by Adsorbing miR-1205 to Facilitate the Progression of Glioma.

This study was aimed at probing into the regulatory effects of circular RNA (circRNA)_0001982 on glioma cell proliferation, migration, invasion, and cell cycle, and its underlying mechanism. CircRNA expression profile of glioma tissues/normal brain tissues was downloaded from the Gene Expression Omnibus (GEO) database and analyzed. Circ_0001982, microRNA (miRNA, miR)-1205, and E2F transcription factor 1 (E2F1) expressions in glioma tissues and cell lines were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) and/or Western blot. Glioma cell proliferation, migration, invasion, and cell cycle were detected employing cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), scratch-healing, Transwell, and flow cytometry assays, respectively. The targeting relationships between miR-1205 and circ_0001982, and miR-1205 and E2F1 3'UTR were verified using bioinformatics, dual-luciferase reporter experiments, and RNA immunoprecipitation (RIP) assay. Pearson's correlation analysis was applied to detect the correlations among circ_0001982, miR-1205, and E2F1 expression levels. Circ_0001982 expression level was increased in glioma tissues and correlated with larger tumor size. Circ_0001982 overexpression enhanced glioma cell proliferation, migration, and invasion, and accelerated cell cycle progression while knocking down circ_0001982 exerted opposite effects. Circ_0001982 directly targeted miR-1205, and miR-1205 directly targeted E2F1. Besides, circ_0001982 could up-regulate E2F1 expression via repressing miR-1205 expression. Circ_0001982 accelerates glioma progression by modulating the miR-1205/E2F1 axis.

Hsa_circ_0137652 Regulates miR-1205/CCNB1 Axis to Accelerate the Malignancy of Breast Cancer.

CircRNAs have become a hotspot in tumor research owing to their high stability and specific functions. We investigated the function of hsa_circ_0137652 in the onset and progression of breast cancer (BC). The expression of circ_0137652, miR-1205, and CCNB1 in BC tissues and cell lines were detected using RT-qPCR and/or western blotting. Dual-luciferase reporter and RNA immunoprecipitation chip assays were used to confirm any potential connections between circ_0137652, miR-1205, and CCNB1. CCK-8 and clone formation assays (CFA) were used to measure the proliferation of BC cells. The Transwell assay was used to investigate the migration of BC cells, and the impact of circ_0137652 on BC tumor formation in vivo was validated using animal experiments. RT-qPCR results showed that circ_0137652 and CCNB1 in breast cancer tissues were notably upregulated in normal tissues, whereas miR-1205 was prominently downregulated. After silencing circ_0137652, the growth and migration of BC cells were reduced. Animal experiments showed that circ_0137652 hampers the tumorigenesis of BC cells in vivo. Additionally, we found that circ_0137652 functions as a sponge for miR-1205. Moreover, the miR-1205 inhibitor notably facilitated cell proliferation and migration and attenuated the action of circ_0137652 knockdown. Furthermore, miR-1205 inhibits BC progression by targeting CCNB1. Circ_0137652 controls the miR-1205/CCNB1 axis to induce increased breast cancer malignancy. Our findings suggest that circ_0137652 may be a novel target for BC therapy.

MicroRNA-1205 Suppresses Hepatocellular Carcinoma Cell Proliferation via a CSNK2B/CDK4 Axis.

Introduction: MicroRNAs (miRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) via modulating expression of their targeting mRNAs. The present study aimed to investigate the role of miR-1205 in HCC cell proliferation and investigate the underlying molecular mechanism. Methods: The effects of miR-1205 on proliferation ability of HCC cell lines were explored in vitro and in vivo. Real-time quantitative PCR (qPCR) analysis was performed to determine miR-1205 expression in HCC tissues and cell lines. Online prediction tools and luciferase assays were used to identify potential target genes of miR-1205. Western blot analysis and dual-luciferase assays were conducted to screen key signaling pathway proteins regulated by miR-1205 and its' target gene. Results: In vitro and in vivo experiments showed that miR-1205 inhibits the proliferation of HCC cells. Dual-luciferase assays showed that miR-1205 interacted with CSNK2B by directly targeting the miRNA-binding site in the CSNK2B sequence, and further qPCR analysis indicated that CSNK2B expression was increased in HCC tissues and negatively correlated with miR-1205 expression. Furthermore, CSNK2B significantly promoted HCC cell proliferation, and CSNK2B overexpression or knockdown attenuated the effects of miR-1205 overexpression or inhibition on HCC cell viability, respectively. Mechanistically, miR-1205 suppresses HCC cell proliferation via a CSNK2B/CDK4 axis. Conclusion: The present results indicated that miR-1205 suppressed HCC cell proliferation by directly targeting CSNK2B and thus inhibiting the CDK4/pRb cell cycle pathway.

Exosomal transfer of circ_0006174 contributes to the chemoresistance of doxorubicin in colorectal cancer by depending on the miR-1205/CCND2 axis.

Exosomes are the mediators of intercellular signal transduction, and they have been involved in the carcinogenesis and chemoresistance of tumor cells. Herein, we intended to investigate whether circular RNA (circRNA) circ_0006174 can regulate chemoresistance of doxorubicin (DOX) in colorectal cancer via exosomes. Forty-one pairs of normal and CRC (DOX sensitive, n = 16; DOX resistant, n = 25) samples were collected. The resistant cell lines (LoVo/DOX and HCT116/DOX) were constructed by exposure of parental cell lines (LoVo and HCT116) to DOX. The detection of circ_0006174, microRNA-1205 (miR-1205), and cyclin D2 (CCND2) was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8(CCK-8) was applied for determining the half of inhibitory concentration (IC50) of DOX and cell proliferation. The migration and invasion capacities were analyzed via transwell assay. Exosomes were extracted using ultracentrifugation. Protein levels were determined using western blot. Dual-luciferase reporter assay was used for affirming target interaction. In vivo experiment was performed by establishing xenograft models in mice. Circ_0006174 level was upregulated in DOX-resistant CRC tissues and cells. The downregulation of circ_0006174 inhibited DOX resistance, cell proliferation, migration, and invasion in DOX-resistant CRC cells. Interestingly, the abundant circ_0006174 was enriched in exosomes derived from DOX-resistant CRC cells. Furthermore, circ_0006174 could enhance DOX resistance via the exosomal intercellular transfer. Moreover, we validated the target relation of circ_0006174/miR-1205 or miR-1205/CCND2. The effect of exosomal circ_0006174 on DOX resistance was achieved by upregulating the miR-1205-mediated CCND2. In vivo, knockdown of circ_0006174 also enhanced tumor sensitivity to DOX by targeting miR-1205/CCND2 axis. Altogether, these findings unraveled that circ_0006174-enriched exosomes elevated DOX chemoresistance in CRC by the miR-1205/CCND2 axis. The exosomal circ_0006174 can be used as an available biomarker for the diagnosis of chemoresistance in CRC.

Circular RNA circ_0000644 promotes papillary thyroid cancer progression via sponging miR-1205 and regulating E2F3 expression.

The dysregulation of circular RNAs (circRNAs) facilitates the tumorigenesis of papillary thyroid carcinoma (PTC). This study was targeted at determining the functions and mechanism of circ_0000644 in regulating PTC development. Circ_0000644, microRNA-1205 (miR-1205) and E2F transcription factor 3 (E2F3) expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Actinomycin D (ActD) and Ribonuclease R (RNase R) assays were used to verify the circular characteristic of circ_0000644. After circ_0000644 was knocked down, PTC cell growth, migration, invasion and apoptosis were assessed by cell counting kit-8 (CCK-8) assay, Transwell assay and flow cytometry analysis, respectively. The regulating relationships among circ_0000644, E2F3 and miR-1205 were confirmed through RNA immunoprecipitation (RIP) assay and dual-luciferase reporter assay. Besides, the regulatory effects of circ_0000644 on the protein level of E2F3 was analyzed via Western blot. In PTC, circ_0000644 was highly expressed, and it was located mainly in the cytoplasm, and it had stable structure. The knockdown of circ_0000644 repressed PTC cell growth, migration, and invasion, and facilitated apoptosis. Circ_0000644 could directly interact with miR-1205 to repress the expression of miR-1205, and it served as a miR-1205 sponge to modulate E2F3 expression in PTC cells. Circ_0000644 up-regulates E2F3 expression via sponging miR-1205 to promote PTC progression.

Circ_0006174 promotes the malignancy of colorectal cancer cell via the miR­1205/CCBE1/Wnt pathway.

Circular RNAs (circRNAs) are novel RNA transcripts that participate in cancer development. Nonetheless, in colorectal cancer (CRC), the information ~circRNA expression and function is largely unknown. The present study aimed to investigate the expression, function and underlying mechanism of circ_0006174 in CRC. Reverse transcription­quantitative PCR analysis was performed to detect circ_0006174, miR­1205 and calcium­binding epidermal growth factor domain­containing protein 1 (CCBE1) expression levels in CRC tissues and cell lines. Circ_0006174 knockdown CRC cell models were established. CCK­8, TUNEL and Transwell methods were utilized to explore the function of circ_0006174 on the malignant phenotype of CRC cells. Moreover, a xenograft nude mouse model was constructed to verify the effects of circ_0006174 on lung metastasis in vivo. Dual­luciferase reporter gene assay was adopted to prove the association between circ_0006174 and miR­1205, miR­1205 and CCBE1. Gene set enrichment analysis was performed using the LinkedOmics database. Western blotting was performed to evaluate the expression of CCBE1, Ki67 and Wnt pathway­related proteins (c­Myc and cyclin D1) in CRC cell lines. Circ_0006174 showed a notable upregulation in CRC tissues and cell lines and its overexpression was linked to larger tumor diameter and advanced T stage of CRC patients. Circ_0006174 knockdown significantly suppressed cell growth and metastatic potential and promoted cell apoptosis in vitro. Circ_0006174 knockdown accelerated the lung metastasis in vivo. Mechanistically, circ_0006174 could decoy miR­1205 to up­modulate CCBE1 expression and Wnt pathway­related proteins (c­Myc and cyclin D1). Circ_0006174 is an oncogenic circRNA, which participates in the promotion of CRC progression by regulating the miR­1205/CCBE1/Wnt pathway.