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

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.

scholarly journals LncRNA LINC00342 contributes to the growth and metastasis of colorectal cancer via targeting miR-19a-3p/NPEPL1

2020 ◽  
Author(s):  
Peng Shen ◽  
Lili Qu ◽  
Jingjing Wang ◽  
Quchen Ding ◽  
Chuanwen Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Protein Coding ◽  
Mechanistic Investigation ◽  
Rna Immunoprecipitation

Abstract Background Long intergenic non-protein coding RNA 342 (LINC00342) has been identified as a novel oncogene, however, the functional role of LINC00342 in colorectal cancer (CRC) remained unclear. Methods The expression of LINC00342 was detected by real-time PCR. Cell proliferation, migration and invasion and xenograft model were examined to analyze the biological functions of LINC00342 in vitro and in vivo. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to identify the target interactions between LINC00342, miR-19a-3p and aminopeptidase like 1 (NPEPL1). Results LINC00342 was highly expressed in CRC. Downregulation of LINC00342 inhibited cell proliferation and metastasis of CRC cells. Moreover, knocking down LINC00342 could weaken the tumor growth in vivo. Mechanistic investigation revealed that LINC00342 may sponge miR-19a-3p to regulate NPEPL1 expression. Further investigation indicated that the oncogenesis facilitated by LINC00342 was inhibited by NPEPL1 depletion.Conclusion LINC00342 promoted CRC progression by competitively binding miR-19a-3p with NPEPL1.

scholarly journals LncRNA LINC00342 contributes to the growth and metastasis of colorectal cancer via targeting miR-19a-3p/NPEPL1 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Peng Shen ◽  
Lili Qu ◽  
Jingjing Wang ◽  
Quchen Ding ◽  
Chuanwen Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Protein Coding ◽  
Mechanistic Investigation

Abstract Background Long intergenic non-protein coding RNA 00342 (LINC00342) has been identified as a novel oncogene. However, the functional role of LINC00342 in colorectal cancer (CRC) remains unclear. Methods The expression of LINC00342 is detected by real-time PCR (RT-PCR) analysis. Cell proliferation, migration and invasion and xenograft model are examined to analyze the biological functions of LINC00342 in vitro and in vivo using colony formation, would healing and transwell analyses. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays are used to identify the target interactions between LINC00342, miR-19a-3p and aminopeptidase like 1 (NPEPL1). Results LINC00342 was highly expressed in CRC. Down-regulation of LINC00342 inhibited cell proliferation and metastasis of CRC cells. Moreover, knocking down LINC00342 inhibited the tumor growth in vivo. Mechanistic investigation revealed that LINC00342 might sponge miR-19a-3p to regulate NPEPL1 expression. Further investigation indicated that the ontogenesis facilitated by LINC00342 was inhibited due to the depletion of NPEPL1. Conclusion LINC00342 promotes CRC progression by competitively binding miR-19a-3p with NPEPL1.

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

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.

scholarly journals LncRNA LINC00342 contributes to the growth and metastasis of colorectal cancer via targeting miR-19a-3p/NPEPL1

2020 ◽  
Author(s):  
Peng Shen ◽  
Lili Qu ◽  
Jingjing Wang ◽  
Quchen Ding ◽  
Chuanwen Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Protein Coding ◽  
Mechanistic Investigation

Abstract Background Long intergenic non-protein coding RNA 00342 (LINC00342) has been identified as a novel oncogene. However, the functional role of LINC00342 in colorectal cancer (CRC) remains unclear. Methods The expression of LINC00342 is detected by real-time PCR (RT-PCR) analysis. Cell proliferation, migration and invasion and xenograft model are examined to analyze the biological functions of LINC00342 in vitro and in vivo using colony formation, would healing and transwell analyses. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays are used to identify the target interactions between LINC00342, miR-19a-3p and aminopeptidase like 1 (NPEPL1). Results LINC00342 was highly expressed in CRC. Down-regulation of LINC00342 inhibited cell proliferation and metastasis of CRC cells. Moreover, knocking down LINC00342 inhibited the tumor growth in vivo. Mechanistic investigation revealed that LINC00342 might sponge miR-19a-3p to regulate NPEPL1 expression. Further investigation indicated that the ontogenesis facilitated by LINC00342 was inhibited due to the depletion of NPEPL1.Conclusion LINC00342 promotes CRC progression by competitively binding miR-19a-3p with NPEPL1.

scholarly journals LncRNA LINC00342 contributes to the growth and metastasis of colorectal cancer via targeting miR-19a-3p/NPEPL1

2020 ◽  
Author(s):  
Peng Shen ◽  
Lili Qu ◽  
Jingjing Wang ◽  
Quchen Ding ◽  
Chuanwen Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Protein Coding ◽  
Mechanistic Investigation ◽  
Rna Immunoprecipitation

Abstract Background Long intergenic non-protein coding RNA 00342 (LINC00342) has been identified as a novel oncogene. However, the functional role of LINC00342 in colorectal cancer (CRC) remains unclear. Methods The expression of LINC00342 was detected by real-time PCR. Cell proliferation, migration and invasion and xenograft model were examined to analyze the biological functions of LINC00342 in vitro and in vivo. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to identify the target interactions between LINC00342, miR-19a-3p and aminopeptidase like 1 (NPEPL1). Results LINC00342 was highly expressed in CRC. Downregulation of LINC00342 inhibited cell proliferation and metastasis of CRC cells. Moreover, knocking down LINC00342 could weaken the tumor growth in vivo. Mechanistic investigation revealed that LINC00342 might sponge miR-19a-3p to regulate NPEPL1 expression. Further investigation indicated that the oncogenesis facilitated by LINC00342 was inhibited due to the depletion of NPEPL1.Conclusion LINC00342 promoted CRC progression by competitively binding miR-19a-3p with NPEPL1.

scholarly journals Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zizhen Si ◽  
Lei Yu ◽  
Haoyu Jing ◽  
Lun Wu ◽  
Xidi Wang
Keyword(s):  
Colorectal Cancer ◽  
Rna Binding ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Cancer Proliferation ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

Abstract Background Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. Currently, the functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. Methods ZNF561-AS1 and SRSF6 expression in CRC patient samples and CRC cell lines was evaluated through TCGA database analysis, western blot along with real-time PCR. SRSF6 expression in CRC cells was also examined upon ZNF561-AS1 depletion or overexpression. Interaction between miR-26a-3p, miR-128-5p, ZNF561-AS1, and SRSF6 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. Small interfering RNA (siRNA) mediated knockdown experiments were performed to assess the role of ZNF561-AS1 and SRSF6 in the proliferative actives and apoptosis rate of CRC cells. A mouse xenograft model was employed to assess tumor growth upon ZNF561-AS1 knockdown and SRSF6 rescue. Results We find that ZNF561-AS1 and SRSF6 were upregulated in CRC patient tissues. ZNF561-AS1 expression was reduced in tissues from treated CRC patients but upregulated in CRC tissues from relapsed patients. SRSF6 expression was suppressed and enhanced by ZNF561-AS1 depletion and overexpression, respectively. Mechanistically, ZNF561-AS1 regulated SRSF6 expression by sponging miR-26a-3p and miR-128-5p. ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 axis was required for CRC proliferation and survival. ZNF561-AS1 knockdown suppressed CRC cell proliferation and triggered apoptosis. ZNF561-AS1 depletion suppressed the growth of tumors in a model of a nude mouse xenograft. Similar observations were made upon SRSF6 depletion. SRSF6 overexpression reversed the inhibitory activities of ZNF561-AS1 in vivo, as well as in vitro. Conclusion In summary, we find that ZNF561-AS1 promotes CRC progression via the miR-26a-3p/miR-128-5p-SRSF6 axis. This study reveals new perspectives into the role of ZNF561-AS1 in CRC.

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 CircSEC24A promotes colorectal cancer progression by regulating miR-488-3p/TMEM106B axis

2020 ◽  
Author(s):  
Gaowu Hu ◽  
Wei Peng ◽  
Yongqing Cao
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Transmembrane Protein ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Cell Progression

Abstract Background: Currently, more and more circular RNAs (circRNAs) have been identified to exert their functions in tumor progression, including colorectal cancer (CRC). However, the role of circSEC24A (circ_0003528) in CRC remains unknown.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the levels of circSEC24A, SEC24A and microRNA-488-3p (miR-488-3p). The characterization of circSEC24A was investigated by Actinomycin D and RNase R digestion assays. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to assess cell proliferation. Flow cytometry analysis was adopted for cell apoptosis and cell cycle process. Transwell assay was employed to evaluate cell migration and invasion. Western blot assay was performed to determine protein levels. Dual-luciferase reporter assay was utilized to explore the relationship between miR-488-3p and circSEC24A or transmembrane protein 106B (TMEM106B). Murine xenograft model was constructed to explore the effect of circSEC24A in vivo .Results: CircSEC24A level was increased in CRC tissues and cells. CircSEC24A deficiency impeded cell proliferation, cell cycle process, migration and invasion and induced apoptosis in CRC cells in vitro and blocked tumorigenesis in vivo . MiR-488-3p was a target of circSEC24A and miR-488-3p was downregulated in CRC tissues and cells. The inhibitory effect of circSEC24A silencing on CRC cell progression was restored by miR-488-3p inhibition. Moreover, TMEM106B could be negatively regulated by miR-488-3p via acting as a downstream gene of miR-488-3p. MiR-488-3p overexpression decelerated CRC cell progression by targeting TMEM106B.Conclusion: CircSEC24A facilitated CRC progression by regulating miR-488-3p/TMEM106B axis, which might provide a promising treatment approach for CRC.

scholarly journals Long Noncoding RNA LINC00958 Suppresses Apoptosis and Radiosensitivity of Colorectal Cancer Through Targeting miR-422a

2021 ◽  
Author(s):  
Hong Liang ◽  
Qiuyan Zhao ◽  
Zhonglin Zhu ◽  
Chao Zhang ◽  
Hui Zhang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
Flow Cytometric ◽  
Potential Biomarker ◽  
Reporter Assays ◽  
Cancer Tissues

Abstract Background: Long non-coding RNAs (lncRNAs) have been elucidated to participate in the development and progression of various cancers. In this study, we aim to explore the underlying functions and mechanisms of LINC00958 in colorectal cancer. Methods: LINC00958 expression in colorectal cancer tissues was examined by qRT-PCR. The associations between LINC00958 expression with clinical characteristics and prognosis were evaluated. The biological functions of LINC00958 were detected by CCK-8, MTT, colony formation and Flow cytometric analyses. RNA-pull down, RIP and luciferase reporter assays were used to confirm the regulation of LINC00958 on miR-422a. Rescue experiments were performed to detect the effects of miR-422a on the roles of LINC00958. Results: LINC00958 was upregulated in colorectal cancer tissues and cell lines; high LINC00958 level was significantly associated with tumor differentiation, T stage and TNM stage, and also predicted poor prognosis. Cell experiments showed that LINC00958 promoted cell proliferation and suppressed apoptosis and the sensitivity of radiotherapy in vitro, and promoted cell growth in vivo. Bioinformatics analysis predicted the binding site of miR-422a on LINC00958. Mechanistically, RNA-pull down, RIP and luciferase reporter assays demonstrated that LINC00958 specially targeted miR-422a. In addition, we provided evidence that miR-422a suppressed MAPK1 expression through directly binding to the 3’-UTR of MAPK1, thereby inhibiting cell proliferation and enhancing apoptosis and the radiosensitivity. Furthermore, miR-422a rescued the roles of LINC00958 on promoting MAPK1 expression and cell proliferation and decreasing apoptosis and the radiosensitivity. Conclusions: LINC00958 promoted MAPK1 expression and cell proliferation and suppressed apoptosis and the radiosensitivity through targeting miR-422a, highlighting a potential biomarker for the prognosis and treatment of colorectal cancer.

scholarly journals Long noncoding RNA RP11-757G1.5 sponges miR-139-5p and upregulates YAP1 thereby promoting the proliferation and liver, spleen metastasis of colorectal cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Xiaojian Zhu ◽  
Fanqin Bu ◽  
Ting Tan ◽  
Qilin Luo ◽  
Jinfeng Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
In Situ Hybridization ◽  
Cox Regression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cox Regression Analysis

Abstract Background Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified. Methods An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivo. Results We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo. Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo. Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development. Conclusions Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.

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