scholarly journals circSLC6A6 Sponges miR-497-5p to Promote Endometrial Cancer Progression via the PI4KB/Hedgehog Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Juan Hu ◽  
Xing Peng ◽  
Weina Du ◽  
Yichuan Huang ◽  
Chun Zhang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Progression ◽  
Hedgehog Pathway ◽  
Luciferase Reporter ◽  
Mechanistic Study ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Ec Cells

Background. As a new kind of noncoding RNAs, circular RNAs (circRNAs) have been substantiated to be involved in multiple biological processes. Accumulating studies indicate that circular RNAs (circRNAs) regulate the development of cancers by acting as miRNA sponges. However, the role of circRNAs in endometrial cancer (EC) is rarely reported. This study was aimed at investigating the functional roles of circSLC6A6 in EC. Methods. The qRT-PCR assay was performed to detect the circSLC6A6 expression in EC tissues and cell lines. The luciferase reporter assay was performed to explore the connection between circSLC6A6 and miR-497-5p as well as the connection between miR-497-5p and PI4KB. The colony formation assay, EdU assay, wound healing assay, and transwell assay were performed to examine the proliferation, migration, and invasion of EC cells. The in vivo assay was performed to reveal the function of circSLC6A6 in tumorigenesis. Results. We found that circSLC6A6 was highly expressed in both EC tissues and cells. And circSLC6A6 promoted the proliferation, migration, and invasion of EC cells in vitro. In vivo, circSLC6A6 promoted tumor growth. Besides, a mechanistic study demonstrated that circSLC6A6 could regulate tumor-associated signaling PI4KB/hedgehog pathway by sponging miR-497-5p. Conclusion. This study illustrates that circSLC6A6 plays a role in promoting EC progression via the miR-497-5p-mediated PI4KB/hedgehog pathway. Our study may provide a potential novel biomarker for EC diagnosis or treatment.

scholarly journals miR-29a-3p inhibits endometrial cancer cell proliferation, migration and invasion by targeting VEGFA/CD C42/PAK1

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aizhi Geng ◽  
Lin Luo ◽  
Fengyun Ren ◽  
Ling Zhang ◽  
Haiying Zhou ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Signaling Pathway ◽  
Scratch Test ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Ec Cells ◽  
Formation Experiment

Abstract Background This study aimed to investigate the mechanism of miR-29a-3p in regulating endometrial cancer (EC) progression. Methods A total of 72 EC patients were enrolled. EC cells were transfected. Cells proliferation, cloning ability, migration and invasion were researched by MTT assay, colony formation experiment, cell scratch test and Transwell experiment respectively. Dual-luciferase reporter assay was performed. Xenograft experiment was conducted using nude mice. miR-29a-3p, VEGFA, CDC42, PAK1 and p-PAK1 expression in cells/tissues was investigated by qRT-PCR and Western blot. Results miR-29a-3p expression was aberrantly reduced in EC patients, which was associated with poor outcome. miR-29a-3p inhibited EC cells proliferation, cloning formation, migration and invasion (P <  0.05 or P <  0.01 or P <  0.001). miR-29a-3p inhibited CDC42/PAK1 signaling pathway activity in EC cells (P <  0.01). VEGFA expression was directly inhibited by miR-29a-3p. miR-29a-3p suppressed EC cells malignant phenotype in vitro and growth in vivo by targeting VEGFA/CDC42/PAK1 signaling pathway (P < 0.05 or P < 0.01). Conclusion miR-29a-3p inhibits EC cells proliferation, migration and invasion by targeting VEGFA/CDC42/PAK1 signaling pathway.

scholarly journals CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Fang Wang ◽  
Xiaochun Wang ◽  
Jingruo Li ◽  
Pengwei Lv ◽  
Mingli Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Cytokine Signaling

Abstract Background Circular RNAs (circRNAs) have caught increasing attentions and interests for their important involvement in cancer initiation and progression. This study aims to investigate the biological functions of circNOL10 and its potential molecular mechanisms in breast cancer (BC). Materials and methods qRT-PCR and western blot assays were performed to measure the expression of related genes. CCK-8, colony formation, flow cytomerty and transwell assays were used to assess cell proliferation, cell cycle, migration and invasion. RNA pull-down, luciferase reporter and RIP assays were applied to address the potential regulatory mechanism of circNOL10. Results CircNOL10 was down-regulated in BC tissues and cells. Low expression of circNOL10 was associated with larger tumor size, advanced TNM stage, lymph node metastasis and unfavorable prognosis. Overexpression of circNOL10 inhibited cell proliferation, migration, invasion and EMT in vitro and slowed xenograft tumor growth in vivo. Mechanistically, circNOL10 could act as a molecular sponge for miR-767-5p, leading to the up-regulation of suppressors of cytokine signaling 2 (SOCS2) and inactivation of JAK2/STAT5 pathway. Moreover, circNOL10-mediated suppression of malignant phenotypes was attenuated by miR-767-5p. Similar to circNOL10, enforced expression of SOCS2 also resulted in the suppression of cell proliferation and metastasis. Furthermore, knockdown of SOCS2 reversed the tumor-suppressive effect induced by circNOL10. Conclusions CircNOL10 repressed BC development via inactivation of JAK2/STAT5 signaling by regulating miR-767-5p/SOCS2 axis. Our findings offer the possibility of exploiting circNOL10 as a therapeutic and prognostic target for BC patients.

scholarly journals Circular RNA circ-ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/p21 axis and acts as a prognostic factor of recurrence

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Junming Bi ◽  
Hongwei Liu ◽  
Wei Dong ◽  
Weibin Xie ◽  
Qingqing He ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Progression ◽  
Tumor Grade ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Rank Test ◽  
Circular Rnas

Abstract Background Circular RNAs (circRNAs) represent a subclass of regulatory RNAs that have been shown to have significant regulatory roles in cancer progression. However, the biological functions of circRNAs in bladder cancer (BCa) are largely unknown. Methods Cell invasion models were established, and invasion-related circRNAs were detected by qPCR. Using above method, circ-ZKSCAN1 was picked out for further study. Circ-ZKSCAN1 expression and survival analyses were performed through qPCR. The survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to assess the significance. Cell proliferation, migration and invasion were examined to investigate the function of circ-ZKSCAN1. Tumorigenesis in nude mice was assessed to determine the effect of circ-ZKSCAN1 in bladder cancer. Biotin-coupled probe pull-down assays, FISH and luciferase reporter assays were conducted to confirm the relationship between circ-ZKSCAN1 and microRNA. RNA-seq revealed different molecular changes in downstream genes. Results Here, we found that circ-ZKSCAN1 was downregulated in BCa tissues and cell lines. Circ-ZKSCAN1 levels were associated with survival, tumor grade, pathological T stage and tumor recurrence. Overexpressed circ-ZKSCAN1 inhibits cell proliferation, migration, invasion and metastasis in vitro and in vivo. Mechanistically, we demonstrated that circ-ZKSCAN1 upregulated p21 expression by sponging miR-1178-3p, which suppressed the aggressive biological behaviors in bladder cancer. Conclusions These results reveal that Circ-ZKSCAN1 acts as a tumor suppressor via a novel circ-ZKSCAN1/miR-1178-3p/p21 axis, which have the important role in the proliferation, migration and invasion ablitities of BCa cells and provide a novel perspective on circRNAs in BCa progression.

scholarly journals Circular RNA 100146 Promotes Colorectal Cancer Progression by miR-149/HMGA2 Axis

2020 ◽  
Author(s):  
Kunpeng Liu ◽  
Yuhua Mou ◽  
Xiufang Shi ◽  
Tingkun Liu ◽  
Zhanfeng Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Xenograft Model ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Western Blot Assay

Aim: Colorectal cancer (CRC) has developed into the third leading reason of cancer-associated death worldwide. Studies has confirmed that circular RNAs (circRNAs) sponge microRNAs (miRNAs) to regulate the function of downstream genes. This study aimed to expound the underlying mechanism of circRNA 100146 in CRC. Methods: The expression of circRNA 100146, miR-149 and high mobility group A2 (HMGA2) was detected by quantitative real time PCR (RT-qPCR). A series of bio-functional effects (cell viability, apoptosis, migration/invasion) were evaluated by methyl thiazolyl tetrazolium (MTT), flow cytometry, transwell. Protein level was measured by Western blot assay. The xenograft model was established for in vivo experiments. The interactions among circRNA 100146, miR-149 and HMGA2 were evaluated by dual-luciferase reporter assay, RNA immunoprecipitation assays, or RNA pulldown assay. Results: CircRNA 100146 was upregulated in CRC tissues and cells. CircRNA 100146 knockdown inhibited cell proliferation, promoted apoptosis and suppressed migration and invasion in vitro, and impeded tumor growth in vivo. Also, miR-149 was negalitively regulated by circRNA 100146, and targeted to HMGA2 and mediated its expression. Moreover, miR-149 interference abrogated the activities of silenced circRNA 100146 in proliferation, apoptosis, migration and invasion. Furthermore, HMGA2 overexpression abated the effects above caused by circRNA 100146 silencing, while the mutant on miR-149 binding sites in HMGA2 3’UTR lead to it losing this ability. Conclusion: CircRNA 100146 knockdown repressed proliferation, enhanced apoptosis and hindered migration and invasion in SW620 and SW480 cells through targeting miR-149/HMGA2 axis.

scholarly journals Circular RNA Circ-0002570 Accelerates Cancer Progression by Regulating VCAN via MiR-587 in Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lei Yang ◽  
Yong-ning Zhou ◽  
Miao-miao Zeng ◽  
Nan Zhou ◽  
Bin-sheng Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Functional Roles ◽  
Reporter Assays

BackgroundCircular RNAs (circRNAs) are closely associated with the occurrences and progress of gastric cancer (GC). We aimed to delve into the function and pathological mechanism of Circular RNA-0002570 (circ-0002570) in GC progression.MethodsCircRNAs differentially expressed in GC were screened using bioinformatics technology. The expression of circ-0002570 was detected in GC specimens and cells via qRT-PCR, and the prognostic values of circ-0002570 were determined. The functional roles of circ-0002570 on proliferation, migration, and invasion in GC cells were explored in vitro and in vivo. Interaction of circ-0002570, miR-587, and VCAN was confirmed by dual-luciferase reporter assays, Western blotting, and rescue experiments.ResultsCirc-0002570 expression was distinctly increased in GC tissues compared to adjacent normal specimens, and GC patients with higher circ-0002570 expressions displayed a short survival. Functionally, knockdown of circ-0002570 resulted in the inhibition of cell proliferation, migration, and invasion, and suppressed tumor growth in vivo. Mechanistically, miR-587 was sponged by circ-0002570. VCAN expression in NSCLC was directly inhibited by miR-587. Overexpression of circ-0002570 prevented VCAN from miR-587-mediated degradation and thus facilitated GC progression.ConclusionThe circ-0002570-miR-587-VCAN regulatory pathway promoted the progression of GC. Our findings provided potential new targets for the diagnosis and therapy of GC.

scholarly journals Circ_0001686 Promotes Prostate Cancer Progression by Up-Regulating SMAD3/TGFBR2 via miR-411-5p

2020 ◽  
Author(s):  
Qiliang Cai ◽  
Jiancheng Pan ◽  
Enli Liang ◽  
Dingrong Zhang ◽  
Cheng Fang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Nude Mouse Model

Abstract Background: Prostate cancer (PCa) is one of the most common malignancies in men. Circular RNAs (circRNAs) are known to be the important regulators in cancer progression. However, the role of circRNAs in PCa is yet to be investigated. Therefore, this study focuses on investigating the effect and the underlying molecular mechanisms of hsa_circ_0001686 (circ_0001686) in PCa. Methods: Sample tissues were collected from the PCa patients to carry out the microarray expression profile of the human circRNAs. In addition, the expression levels of circ_0001686, has_miR-411-5p (miR-411-5p), SMAD3, and TGFBR2 were also detected by qRT-RCR. Next, transfection experiments were employed to measure the effect of circ_0001686 on cell proliferation, migration, and invasion in the PCa cell lines (CWR22RV1and LNCaP). These effects were analyzed using MTT, colony formation, transwell, and scratch wound assays, respectively. The si-circ_0001686 was used as a negative control. Starbase and TargetScan databases were used to predict the putative binding sites among circ_0001686, miR-411-5p, and SMAD3/TGFBR2. The dual-luciferase reporter assays were performed to verify these interactions. Furthermore, the levels of SMAD3 and TGFBR2 in CWR22RV1 and LNCaP cells were measured by western blot. Finally, in vivo experiments in the nude mouse model were carried out to strengthen the in vitro findings. Results: The expression of circ_0001686 was markedly up-regulated while the expression of miR-411-5p was down-regulated in PCa cells. Moreover, circ_0001686 promoted cell proliferation, migration, and invasion. Molecular mechanism exploration revealed that circ_0001686 acts as a sponge of miR-411-5p which affects the downstream target gene SMAD3, and TGFBR2. Both the in vitro and in vivo studies verified that miR-411-5p inhibits cancer growth and metastasis in PCa.Conclusions: The circ_0001686 sequesters miR-411-5p to increase the expression of SMAD3/TGFBR2 which consequently promotes the proliferation, invasion, and migration in PCa cells.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

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

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Jingpeng Wang ◽  
Shuyuan Li ◽  
Gaofeng Zhang ◽  
Huihua Han
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Volatile Anesthetic ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas

Abstract 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.

scholarly journals Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qun Dai ◽  
Jingyi Deng ◽  
Jinrong Zhou ◽  
Zhuhong Wang ◽  
Xiao-feng Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Marked Rise ◽  
Hcc Cells

Abstract Background Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. Methods The expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo. Results We found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2. Conclusion TUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.

scholarly journals Long Non-coding RNA SNHG25 Promotes the Malignancy of Endometrial Cancer by Sponging microRNA-497-5p and Thereby Increasing FASN Expression

2021 ◽  
Author(s):  
Yuhua He ◽  
Shuifang Xu ◽  
Yi Qi ◽  
Jinfang Tian ◽  
Fengying Xu
Keyword(s):  
Endometrial Cancer ◽  
Noncoding Rna ◽  
Fatty Acid Synthase ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Molecular Events ◽  
Ec Cells ◽  
High Level

Abstract BackgroundSmall nucleolar RNA host gene 25 (SNHG25), a long-noncoding RNA, has been well studied in epithelial ovarian cancer. Yet, the specific functions of SNHG25 in endometrial cancer (EC) have not been researched. In this study, we proposed to expose the clinic significance of SNHG25 in EC, and then unravel the regulatory activity of SNHG25 on the tumor-associated phenotype of EC. More interestingly, the possible molecular events occurred when SNHG25 executives its function in EC were explored thoroughly. MethodsWe measured genes expression applying quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined employing loss-of-function experiments. What’s more, we unveiled the regulatory mechanisms among SNHG25, microRNA-497-5p and fatty acid synthase (FASN) with the application of luciferase reporter assay and RNA Immunoprecipitation. ResultsWe verified a high level of SNHG25 in EC through TCGA dataset and our own cohort. Patients with a high SNHG25 level featured shorter overall survival in contrast to patients with a low SNHG25 level. SNHG25 deficient caused tumor-repressing actions in EC cells by decreasing cell proliferation, migration and invasion and promoting cell apoptosis. Furthermore, we certified the function of SNHG25 depletion in impairing tumor growth in vivo. With respect to the mechanisms, SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Striking, the decrease of miR-497-5p or increase of FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. ConclusionsDepleted SNHG25 hampered the oncogenicity of EC by targeting miR-497-5p/FASN axis. The newly certified SNHG25/miR-497-5p/FASN pathway may potentially have usefulness as a promising target for molecular targeted management.

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