The Experts below are selected from a list of 13062 Experts worldwide ranked by ideXlab platform
Xiang Fang - One of the best experts on this subject based on the ideXlab platform.
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microrna 20a 5p suppresses tumor angiogenesis of non small cell lung cancer through RRM2 mediated pi3k akt signaling pathway
Molecular and Cellular Biochemistry, 2021Co-Authors: Junlei Han, Fang Sun, Hongzhi Bian, Bingxiang Tang, Xiang FangAbstract:The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.
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MicroRNA-20a-5p suppresses tumor angiogenesis of non-small cell lung cancer through RRM2-mediated PI3K/Akt signaling pathway
Molecular and cellular biochemistry, 2020Co-Authors: Junlei Han, Fang Sun, Hongzhi Bian, Bingxiang Tang, Xiang FangAbstract:The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.
Junlei Han - One of the best experts on this subject based on the ideXlab platform.
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microrna 20a 5p suppresses tumor angiogenesis of non small cell lung cancer through RRM2 mediated pi3k akt signaling pathway
Molecular and Cellular Biochemistry, 2021Co-Authors: Junlei Han, Fang Sun, Hongzhi Bian, Bingxiang Tang, Xiang FangAbstract:The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.
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MicroRNA-20a-5p suppresses tumor angiogenesis of non-small cell lung cancer through RRM2-mediated PI3K/Akt signaling pathway
Molecular and cellular biochemistry, 2020Co-Authors: Junlei Han, Fang Sun, Hongzhi Bian, Bingxiang Tang, Xiang FangAbstract:The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.
Yun Yen - One of the best experts on this subject based on the ideXlab platform.
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Abstract 3677: Nanoparticle mediated delivery of siRNA targeting RRM2 inhibits tumor growth of head and neck and lung cancers
Cancer Chemistry, 2010Co-Authors: Mohammad Aminur Rahman, Yun Yen, Dongsheng Wang, A.r.m. Ruhul Amin, Zhuo Georgia Chen, Bingsen Zhou, Mark E Davis, Xu Wang, Dong M. ShinAbstract:Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Inhibition of specific genes by small interfering RNAs (siRNA) offers a promising therapeutic approach in oncology. However, siRNA therapy is hindered by poor stability under physiological conditions and limited intracellular uptake. Ribonucleotide reductase subunit M2 (RRM2) is an essential protein for DNA synthesis and is responsible for the reduction of ribonucleotides to deoxyribonucleotides, providing a balanced supply of precursors for DNA synthesis and repair. In this study we investigated the efficacy and mechanism of action of a targeted nanoparticle formulation of siRNA against RRM2. The clinical version of this nanoparticle is denoted as CALAA-01 and is currently used in a Phase I clinical trial. The nanoparticle consists of a cyclodextrin-containing polymer, a polyethylene glycol steric stabilization agent, and human transferrin as a targeting ligand for binding to transferrin receptors (TfR) that are typically up regulated in cancer cells. Initially, we screened several head and neck squamous cell carcinoma (HNSCC) and lung cancer cell lines and found various degrees of expression of TfR and RRM2. Suppression of RRM2 by transfection of 5 nM siRNA for 72 hours in vitro strongly inhibited the cell growth in HNSCC (Tu212∼75% and M4e∼60%) and in lung cancer cell lines (A549 and H460 ∼80%). Using xenograft (Tu212) as an in-vivo model, we found nanoparticles (10mg/Kg) injected via the tail vein in four dosing schedules (Day 1, 3, 8 and 10) significantly reduced RRM2 expression and its activity in xenograft tumors. RRM2 activity was reduced by an average 1.88-fold in the RRM2 siRNA treated group compare to the formulated control siRNA group (p=0.04). We monitored tumor growth in treated and control groups (8 mice in each group) for 28 days and found that tumor growth reduced by an average 2.9- fold in the treated group compared to formulated control siRNA (p=0.004). The nanoparticle delivered RRM2 siRNA significantly suppressed cell proliferation and induced apoptosis as evidenced by xenograft tumor tissue staining with Ki67 and terminal deoxynucleotidyl transferase dUTP nick and labeling, respectively. Mechanistic studies (in-vitro) have revealed siRNA-mediated suppression of RRM2 increases apoptosis in a p53-independent manner. Interestingly, suppression of RRM2 by 5nM siRNA for 72 hours increased activation of caspase 9 and caspase 3 at least 2-fold with concomitant increase in the levels of cleaved poly-ADP-ribose polymerase (PARP), thus suggesting a vital role for p73 in the observed apoptosis through an intrinsic pathway. Thus this study demonstrates that targeted nanoparticles can deliver RRM2 siRNA to head and neck tumors in mice and highlights RRM2 as an excellent target to induce potent apoptosis and tumor growth inhibition. (Supported by NIH/NCI grant U54CA119338-04) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3677.
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Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis.
Molecular cancer, 2009Co-Authors: Keqiang Zhang, Xiyong Liu, Linling Chen, Bingsen Zhou, Xiaochen Wang, Yun YenAbstract:Background In addition to its essential role in ribonucleotide reduction, ribonucleotide reductase (RNR) small subunit, RRM2, has been known to play a critical role in determining tumor malignancy. Overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor. Angiogenesis is critical to tumor malignancy; it plays an essential role in tumor growth and metastasis. It is important to investigate whether the angiogenic potential of tumor is affected by RRM2.
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RRM2 increases MMP9 mRNA expresssion, decreases TSP1 mRNA expression in human oropharyngeal carcinoma KB cells
Cancer Research, 2008Co-Authors: Keqiang Zhang, Xiyong Liu, Linling Chen, Bingshen Zhou, Yun YenAbstract:1135 Ribonucleotide Reductase (RR) is an enzyme that catalyzes de novo conversion of ribonucleotide 59-diphosphates to their 29-deoxynucleotide forms. It is a rate-limiting step in the production of 29-deoxyribonucleoside 59-triphosphates required for DNA synthesis. RR consists of two subunits, RRM1 and RRM2. RRM2 subunit has been known to function as the catalytic domain of RR. Futher studies also have shown that RRM2 plays important roles in cell proliferation, invasiveness, metastasis and drug resistance. To explore the causative role of RRM2 in invasion and metastasis, we examined the RRM2 overexpression transfectant in human oropharyngeal carcinoma KB cells. Using the quantitative RT-PCR, we demonstrated that overexpression of RRM2 results in increase of MMP2, MMP9 and TIMP2 mRNA expression, while it decreases TSP1 mRNA expression. Gelatin Zymography assay showed that the activities of MMP2 and MMP9 are also induced by RRM2 overexpression. This study may shed light on the mechanism of RRM2 in the regulation of tumor invasion and metastasis.
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potent sirna inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo
Clinical Cancer Research, 2007Co-Authors: Jeremy D Heidel, Yun Yen, Joanna Yi Ching Liu, Bingsen Zhou, Bret S E Heale, John J Rossi, Derek W Bartlett, Mark E DavisAbstract:Purpose: Ribonucleotide reductase (RR) is a therapeutic target for DNA replication–dependent diseases such as cancer. Here, a potent small interfering RNA (siRNA) duplex against the M2 subunit of RR (RRM2) is developed and shown to reduce the growth potential of cancer cells both in vitro and in vivo . Experimental Design: Three anti-RRM2 siRNAs were identified via computational methods, and the potency of these and additional “tiling” duplexes was analyzed in cultured cells via cotransfections using a RRM2-luciferase fusion construct. Knockdown of RRM2 by the best duplex candidates was confirmed directly by Western blotting. The effect of potent duplexes on cell growth was investigated by a real-time cell electronic sensing assay. Finally, duplex performance was tested in vivo in luciferase-expressing cells via whole animal bioluminescence imaging. Results: Moderate anti-RRM2 effects are observed from the three duplexes identified by computational methods. However, the tiling experiments yielded an extremely potent duplex (siR2B+5). This duplex achieves significant knockdown of RRM2 protein in cultured cells and has pronounced antiproliferative activity. S.c. tumors of cells that had been transfected with siR2B+5 preinjection grew slower than those of control cells. Conclusions: An anti-RRM2 siRNA duplex is identified that exhibits significant antiproliferative activity in cancer cells of varying human type and species (mouse, rat, monkey); these findings suggest that this duplex is a promising candidate for therapeutic development.
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human ribonucleotide reductase m2 subunit gene amplification and transcriptional regulation in a homogeneous staining chromosome region responsible for the mechanism of drug resistance
Cytogenetic and Genome Research, 2001Co-Authors: B Zhou, Xiyong Liu, W Qiu, Yun YenAbstract:In our previous publication it was shown that a Gemcitabine-resistant KBGem clone derived from step-wise exposure to Gemcitabine resulted in overexpression of the human Ribonucleotide Reductase M2 subunit (hRRM2) mRNA and protein (Goan et al., 1999). In this study we confirm these results and show that the hRRM2 gene amplification arises in a homogeneous staining region (hsr) derived from chromosome translocation. The hydroxyurea-resistant clone (KBHURs) was studied as a comparison. PCR analysis of the hRRM2 gene promoter confirmed the amplification. Northern and Western blots were further employed to confirm the gene amplification and hRRM2 mRNA and protein expression were compatible with the level of drug resistance. Cells synchronized by serum starvation and then returned to serum-containing growth conditions showed a rapid induction of high levels of transcription of the hRRM2 gene. To clarify whether expression of hRRM2 mRNA was regulated at a transcriptional level, several transcription factors, including AP-1, Sp1, AP-2, CREB, NF-kappa B, and OCT1, were examined by gel-shift assay. Interestingly, the KBGem clone was regulated by different transcription factors than the KBHURs clone. Compared to the wild-type KB cells (KBwt), the KBGem clone exhibited a different binding pattern for Sp1 and NF-kappa B. The KBHURs clone, however, demonstrated a unique binding pattern with AP-1 and CREB, different from the KBwt control as well as the KBGem clone. Therefore, we conclude that the drug-resistant phenotype is associated with human RRM2 gene amplification from a homogeneous staining chromosome region and altered transcription regulation. Each clone demonstrated a unique pattern of transcription factor binding that may play a vital role in the mechanism of drug resistance.
Hongzhi Bian - One of the best experts on this subject based on the ideXlab platform.
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microrna 20a 5p suppresses tumor angiogenesis of non small cell lung cancer through RRM2 mediated pi3k akt signaling pathway
Molecular and Cellular Biochemistry, 2021Co-Authors: Junlei Han, Fang Sun, Hongzhi Bian, Bingxiang Tang, Xiang FangAbstract:The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.
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MicroRNA-20a-5p suppresses tumor angiogenesis of non-small cell lung cancer through RRM2-mediated PI3K/Akt signaling pathway
Molecular and cellular biochemistry, 2020Co-Authors: Junlei Han, Fang Sun, Hongzhi Bian, Bingxiang Tang, Xiang FangAbstract:The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.
Bingxiang Tang - One of the best experts on this subject based on the ideXlab platform.
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microrna 20a 5p suppresses tumor angiogenesis of non small cell lung cancer through RRM2 mediated pi3k akt signaling pathway
Molecular and Cellular Biochemistry, 2021Co-Authors: Junlei Han, Fang Sun, Hongzhi Bian, Bingxiang Tang, Xiang FangAbstract:The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.
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MicroRNA-20a-5p suppresses tumor angiogenesis of non-small cell lung cancer through RRM2-mediated PI3K/Akt signaling pathway
Molecular and cellular biochemistry, 2020Co-Authors: Junlei Han, Fang Sun, Hongzhi Bian, Bingxiang Tang, Xiang FangAbstract:The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.
