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

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

10.21203/rs.3.rs-42527/v1 ◽

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.

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

Molecular Cancer ◽

10.1186/s12943-019-1060-9 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 22

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.

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

Journal of Biological Research-Thessaloniki ◽

10.1186/s40709-021-00145-6 ◽

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.

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miR-362-3p acts as a tumor suppressor by targeting SERBP1 in ovarian cancer

Journal of Ovarian Research ◽

10.1186/s13048-020-00760-2 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Shujun Cao ◽

Na Li ◽

Xihong Liao

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Progression ◽

Target Gene ◽

Molecular Mechanisms ◽

Gynecological Cancer ◽

Luciferase Reporter ◽

Loss Of Function

Abstract Background Ovarian cancer is the leading lethal gynecological cancer and is generally diagnosed during late-stage presentation. In addition, patients with ovarian cancer still face a low 5-year survival rate. Thus, innovative molecular targeting agents are required to overcome this disease. The present study aimed to explore the function of miR-362-3p and the underlying molecular mechanisms influencing ovarian cancer progression. Methods The expression levels of miR-362-3p were determined using qRT-PCR. Gain-of-function and loss-of-function methods were used to detect the effects of miR-362-3p on cell proliferation, cell migration, and tumor metastasis in ovarian cancer. A luciferase reporter assay was performed to confirm the potential target of miR-362-3p, and a rescue experiment was employed to verify the effect of miR-362-3p on ovarian cancer by regulating its target gene. Results miR-362-3p was significantly downregulated in ovarian cancer tissues and cell lines. In vitro, our data showed that miR-362-3p suppressed cell proliferation and migration. In vivo, miR-362-3p inhibited ovarian cancer growth and metastasis. Mechanistically, SERBP1 was identified as a direct target and functional effector of miR-362-3p in ovarian cancer. Moreover, SERBP1 overexpression rescued the biological function of miR-362-3p. Conclusions Our data reveal that miR-362-3p has an inhibitory effect on ovarian cancer. miR-362-3p inhibits the development and progression of ovarian cancer by directly binding its target gene SERBP1.

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LncRNA LINC00342 promotes gastric cancer progression by targeting the miR-545-5p/CNPY2 axis

BMC Cancer ◽

10.1186/s12885-021-08829-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Run Liu ◽

Xianwu Yang

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Growth Factor Signaling ◽

Ags Cells

Abstract Background This study aimed to explore the role and underlying molecular mechanisms of long non-coding RNA (lncRNA) LINC00342 in gastric cancer (GC). Methods The expression of LINC00342 in GC tissues was evaluated by Quantitative reverse transcription polymerase chain reaction (qRT-PCR). Silencing of LINC00342 was conducted to investigate the effect of LINC00342 in vitro and in vivo. The underlying molecular mechanisms of LINC00342 were determined by dual luciferase reporter assay, Western blotting analysis and rescue experiments. Biological functions of LINC00342 were evaluated by cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay and Transwell assays. In addition, a tumor model was used to verify the effect of LINC00342 in tumorigenesis in vivo. Results LINC00342 was significantly upregulated in GC tissues and cell lines. Silencing of LINC00342 efficiently inhibited proliferation, migration and invasion of AGS cells in vitro, and also suppressed the tumorigenesis of GC in vivo. Functional experiments showed that LINC00342 regulated the expression of canopy fibroblast growth factor signaling regulator 2 (CNPY2) by competitively sponging miR-545-5p. Rescue experiments showed that inhibition of miR-545-5p and overexpression of CNPY2 significantly reversed cell phenotypes caused by silencing of LINC00342. Conclusion LINC00342 plays a potential oncogenic role in GC by targeting the miR545-5p/CNPY2 axis, and might act as a novel therapeutic target for GC.

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Hsa_circ_0026416 promotes proliferation and migration in colorectal cancer via miR-346/NFIB axis

Cancer Cell International ◽

10.1186/s12935-020-01593-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yahang Liang ◽

Jingbo Shi ◽

Qingsi He ◽

Guorui Sun ◽

Lei Gao ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Molecular Mechanisms ◽

Xenograft Model ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Potential Biomarker ◽

Mouse Xenograft Model

Abstract Background Colorectal cancer (CRC) is one of the most common cancers worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been confirmed to be key regulators of many diseases. With many scholars devoted to studying the biological function and mechanism of circRNAs, their mysterious veil is gradually being revealed. In our research, we explored a new circRNA, hsa_circ_0026416, which was identified as upregulated in CRC with the largest fold change (logFC = 3.70) of the evaluated circRNAs via analysing expression profiling data by high throughput sequencing of members of the GEO dataset (GSE77661) to explore the molecular mechanisms of CRC. Methods qRT-PCR and western blot analysis were utilized to assess the expression of hsa_circ_0026416, miR-346 and Nuclear Factor I/B (NFIB). CCK-8 and transwell assays were utilized to examine cell proliferation, migration and invasion in vitro, respectively. A luciferase reporter assay was used to verify the combination of hsa_circ_0026416, miR-346 and NFIB. A nude mouse xenograft model was also utilized to determine the role of hsa_circ_0026416 in CRC cell growth in vivo. Results Hsa_circ_0026416 was markedly upregulated in CRC patient tissues and plasma and was a poor prognosis in CRC patients. In addition, the area under the curve (AUC) of hsa_circ_0026416 (0.767) was greater than the AUC of CEA (0.670), CA19-9 (0.592) and CA72-4 (0.575). Functionally, hsa_circ_0026416 promotes cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, hsa_circ_0026416 may function as a ceRNA via competitively absorbing miR-346 to upregulate the expression of NFIB. Conclusions In summary, our findings demonstrate that hsa_circ_0026416 is an oncogene in CRC. Hsa_circ_0026416 promotes the progression of CRC via the miR-346/NFIB axis and may represent a potential biomarker for diagnosis and therapy in CRC.

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EIF4A3-induced circ_0084615 contributes to the progression of colorectal cancer via miR-599/ONECUT2 pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02029-y ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Zhipeng Jiang ◽

Qinwen Tai ◽

Xiaojun Xie ◽

Zehui Hou ◽

Wei Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Xenograft Model ◽

Tube Formation ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Western Blot Assay

Abstract Background Colorectal cancer (CRC) is a common malignant tumor. Circular RNAs (circRNAs) have been reported to take part in the progression of CRC. However, the functions of circ_0084615 in CRC development are still undefined. In this study, we aimed to explore the functions and underlying mechanisms of circ_0084615 in CRC. Methods qRT-PCR, western blot assay and IHC assay were utilized for the levels of circ_0084615, miR-599, ONECUT2 or EIF4A3. 5-ethynyl-2’-deoxyuridine (EdU) assay and colony formation assay were conducted for cell proliferation ability. Wound-healing assay and transwell assay were applied to evaluate cell migration and invasion. Tube formation assay was used to analyze angiogenesis ability. RNA immunoprecipitation (RIP) assay, RNA pull down assay and dual-luciferase reporter assay were used to analyze the relationships of circ_0084615, miR-599, ONECUT2 and EIF4A3. Murine xenograft model assay was employed for the role of circ_0084615 in vivo. Results Circ_0084615 was elevated in CRC tissues and was linked to TNM stages, lymph node metastasis, differentiation and overall survival rate. Circ_0084615 knockdown inhibited CRC cell proliferation, migration, invasion and angiogenesis in vitro and hampered tumorigenesis in vivo. Circ_0084615 sponged miR-599 and miR-599 inhibition reversed circ_0084615 knockdown-mediated effects on CRC cell growth, motility and angiogenesis. ONECUT2 was identified as the target gene of miR-599. ONECUT2 overexpression recovered the effects of miR-599 on CRC malignant behaviors. Additionally, EIF4A3 induced circ_0084615 expression. Conclusions EIF4A3-induced circ_0084615 played an oncogenic role in CRC development via miR-599/ONECUT2 axis.

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EGR1 Modulated LncRNA HNF1A-AS1 Drives Glioblastoma Progression Via miR-22-3p/ENO1 Axis

10.21203/rs.3.rs-477104/v1 ◽

2021 ◽

Author(s):

Chunchun Ma ◽

Hongliang Wang ◽

Gang Zong ◽

Jie He ◽

Yuyang Wang ◽

...

Keyword(s):

Cell Proliferation ◽

Molecular Mechanisms ◽

Bioinformatic Analysis ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Clinical Samples ◽

Regulation Mechanism ◽

Functional Studies

Abstract Background: Accumulating evidences revealed that long noncoding RNAs (lncRNAs) have been participated in cancer malignant progression, including glioblastoma multiforme (GBM). Despite much studies have found the precise biological role in the regulatory mechanisms of GBM，however the molecular mechanisms，particularly upstream mechanisms still need further elucidated. Methods: RT-QPCR, cell transfection, western blotting and bioinformatic analysis were executed to detect the expression of EGR1, HNF1A-AS1, miR-22-3p and ENO1 in GBM. Cell proliferation assay, colony formation assay, wound healing, migration and invasion assays were performed to detect the malignant characters of GBM cell. The molecular regulation mechanism was confirmed by luciferase reporter assay, ChIP and RIP. Finally, orthotopic mouse models were established to examine the effect of HNF1A-AS1 in vivo.Results: In the current study, we analyzed clinical samples to show that the long non-coding antisense transcript of HNF1A, HNF1A-AS1, is upregulated and associated with poor prognosis in GBM. Functional studies revealed that knockdown of HNF1A-AS1 markedly inhibits cell proliferation, migration and invasion both in vitro and in vivo, whereas overexpression of HNF1A-AS1 exerts opposite effect. Mechanistically, the transcription factor EGR1 forced the transcription of HNF1A-AS1 by directly binding the promoter region of HNF1A-AS1. Furthermore, combined bioinformatics analysis with our mechanistic work, using luciferase reporter assays and RIP, we first demonstrated that HNF1A-AS1 functions as a competing endogenous RNA (ceRNA) with miR-22-3p to regulate ENO1 expression in GBM cells. HNF1A-AS1 directly binds to miR-22-3p and significantly inhibits miR-22-3p expression, while ENO1 expression was increased. miR-22-3p inhibitor offsets the HNF1A-AS1 silencing induced suppression in proliferation, migration and invasion of GBM cells, as well as promotion effect on ENO1 expression. ENO1 was verified as a direct target of miR-22-3p and its expression levels was negatively with the prognosis in GBM patients. Conclusion: Taken together, our study illuminated the definite mechanism of HNF1A-AS1 in promoting GBM malignancy, and provided a novel therapeutic target for further clinical application.

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

Journal of Immunology Research ◽

10.1155/2021/5512391 ◽

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.

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LncRNA LINC00337 sponges mir-1285-3p to promote proliferation and metastasis of lung adenocarcinoma cells by upregulating YTHDF1

Cancer Cell International ◽

10.1186/s12935-021-02253-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ru-nan Zhang ◽

Dong-mei Wu ◽

Li-ping Wu ◽

Guo-wei Gao

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Gear Up ◽

Underlying Mechanisms

Abstract Background Emerging studies have shown that long noncoding RNAs (lncRNAs) predominantly function in the carcinogenesis of multiple developing human tumors. The current study aimed to investigate the underlying mechanisms of LINC00337 in lung adenocarcinoma. Methods We analyzed TCGA and GTEx datasets and chose LINC00337 as the research object. Cell proliferation, cell apoptosis, cell cycle, migration, and invasion were detected in the gain and loss experiments of LINC00337 both in vitro and in vivo. Moreover, RNA pull-down, luciferase reporter assays, western blotting analysis, and rescue experiments were performed to investigate the underlying molecular mechanisms of LINC00337 function. Results LINC00337 expression was remarkably upregulated in lung adenocarcinoma. In addition, LINC00337 knockdown was shown to repress cell migration, invasion, and proliferation, as well as the cell cycle, and gear up apoptosis in lung adenocarcinoma in vitro and in vivo. With respect to the mechanism, LINC00337 knockdown boosted miR-1285-3p expression and then restrained YTHDF1 expression post-transcriptionally. Crucially, both miR-1285-3p decrement and YTHDF1 overexpression successfully reversed the influence on cell proliferation, migration, invasion, and apoptosis caused by LINC00337 shRNA. Conclusions These results suggest that LINC00337 acts as an oncogenic lncRNA, targeting miR-1285-3p and regulating YTHDF1 expression, to promote the progression of lung adenocarcinoma.

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