scholarly journals LINC01006 influences cell proliferation, apoptosis, migration and invasion by targeting miR-34a-5p/DAAM1 in prostate cancer

2020 ◽  
Author(s):  
Enhui Ma ◽  
Qianqian Wang ◽  
Jinhua Li ◽  
Xinqi Zhang ◽  
Zhenjia Guo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Tumor Suppressors ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Functional Assay ◽  
Inhibitory Effects ◽  
Downstream Targets ◽  
The Relationship ◽  
Oncogenic Function

Abstract Background: Large quantities of researches have demonstrated that long noncoding RNAs (lncRNAs) exert crucial function in the development of human cancers by acting as oncogenes or tumor suppressors. LINC01006 was once found to have oncogenic function in pancreatic cancer. However, its role is still unclear in prostate cancer (PCa).Methods: RT-qPCR assay examined LINC01006, miR-34a-5p, DAAM1 expression in PCa cells. RNA pull down and luciferase reporter assay were used to certify the relationship between LINC01006 and its downstream targets.Results: LINC01006 was discovered to be remarkably high in PCa cell lines. Moreover, the functional assay validated that LINC01006 silence hindered proliferation, migration and invasion as well as accelerated apoptosis in PCa cells. The results of nucleus cytoplasm fractionation and FISH assay revealed that LINC01006 had the possibility to modulate downstream targets in ceRNA mechanism. MiR-34a-5p was selected out to be low expressed in PCa cell lines. In addition, miR-34a-5p up-regulation restricted proliferative, migratory and invaded capacities while facilitated apoptosis in PCa cells. DAAM1 was determined to be negatively regulated by miR-34a-5p. More interestingly, DAAM1 knockdown had inhibitory effects on PCa cells. Eventually, data of rescue assays exhibited that overexpression of DAAM1 countervailed the suppressive impacts of LINC01006 down-regulation on PCa progression.Conclusions: LINC01006 was an oncogene in PCa by targeting miR-34a-5p/DAAM1, which offered a novel insight for treating PCa.

scholarly journals The COX10-AS1/miR-641/E2F6 feedback loop is involved in the progression of glioma

2020 ◽  
Author(s):  
Liang Liu ◽  
Xiaojian Li ◽  
Heming Wu ◽  
Yong Tang ◽  
Xiang Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Feedback Loop ◽  
Primary Tumour ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Biological Processes ◽  
Tumour Xenograft ◽  
Reporter Assays ◽  
The Central Nervous System ◽  
The Relationship

Abstract Background Glioma is the most common primary tumour of the central nervous system and is considered one of the greatest challenges for neurosurgery. Mounting evidence has shown that lncRNAs participate in various biological processes of tumours, including glioma. This study aimed to reveal the role and relevant mechanism of COX10-AS1 in glioma. Methods The expression of COX10-AS1, miR-641 and E2F6 was measured by qRT-PCR and/or western blot. Clone formation assays, EdU assays, Transwell assays and tumour xenograft experiments were performed to evaluate the effects of COX10-AS1, miR-641 and E2F6 on glioma proliferation, migration and invasion. Luciferase reporter assays, RNA pull-down assays and ChIP assays were conducted to analyse the relationship among COX10-AS1, miR-641 and E2F6. Results First, we demonstrated that COX10-AS1 was upregulated in glioma tissues and cell lines, which was related to the grade of glioma and patient survival. Next, through functional assays, we found that COX10-AS1 influenced the proliferation, migration and invasion of glioma cell lines. Then, with the help of bioinformatics analysis, we confirmed that COX10-AS1 regulated glioma by acting as a sponge of miR-641 to regulate E2F6. Moreover, further study indicated that E2F6 could promote COX10-AS1 expression by binding to its promoter region. Conclusions COX10-AS1 acts as an oncogene in combination with COX10-AS1/miR-641/E2F6 in glioma, which may be beneficial to the diagnosis and treatment of glioma.

scholarly journals microRNA-802 inhibits epithelial-mesenchymal transition through targeting flotillin-2 in human prostate cancer

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Dawei Wang ◽  
Guoliang Lu ◽  
Yuan Shao ◽  
Da Xu
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

miRNAs are a class of non-coding RNAs that exert critical roles in various biological processes. The aim of the present study was to identify the functional roles of miR-802 in regulating epithelial–mesenchymal transition (EMT) in prostate cancer (PCa). miR-802 expression was detected in 73 pairs of PCa samples and PCa cell lines (PC3 and DU145 cells) by qRT-PCR. Cell proliferation was detected using MTT assay, and cell apoptosis was evaluated using flow cytometry. Transwell assay was conducted to investigate cell migration and invasion. Expression analysis of a set of EMT markers was performed to explore whether miR-802 is involved in EMT program. Xenograft model was established to investigate the function of miR-802 in carcinogenesis in vivo. The direct regulation of Flotillin-2 (Flot2) by miR-802 was identified using luciferase reporter assay. miR-802 was remarkably down-regulated in PCa tissues and cell lines. Gain-of-function trails showed that miR-802 serves as an ‘oncosuppressor’ in PCa through inhibiting cell proliferation and promoting cell apoptosis in vitro. Overexpression of miR-802 significantly suppressed in vivo PCa tumor growth. Luciferase reporter analysis identified Flot2 as a direct target of miR-802 in PCa cells. Overexpressed miR-802 significantly suppressed EMT, migration and invasion in PCa cells by regulating Flot2. We identified miR-802 as a novel tumor suppressor in PCa progression and elucidated a novel mechanism of the miR-802/Flot2 axis in the regulation of EMT, which may be a potential therapeutic target.

scholarly journals The COX10-AS1/miR-641/E2F6 Feedback Loop Is Involved in the Progression of Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Liang Liu ◽  
Xiaojian Li ◽  
Heming Wu ◽  
Yong Tang ◽  
Xiang Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Feedback Loop ◽  
Primary Tumour ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Biological Processes ◽  
Tumour Xenograft ◽  
Reporter Assays ◽  
The Central Nervous System ◽  
The Relationship

Glioma is the most common primary tumour of the central nervous system and is considered one of the greatest challenges for neurosurgery. Mounting evidence has shown that lncRNAs participate in various biological processes of tumours, including glioma. This study aimed to reveal the role and relevant mechanism of COX10-AS1 in glioma. The expression of COX10-AS1, miR-641 and E2F6 was measured by qRT-PCR and/or western blot. Clone formation assays, EdU assays, Transwell assays and tumour xenograft experiments were performed to evaluate the effects of COX10-AS1, miR-641 and E2F6 on glioma proliferation, migration and invasion. Luciferase reporter assays, RNA pull-down assays and ChIP assays were conducted to analyse the relationship among COX10-AS1, miR-641 and E2F6. We demonstrated that COX10-AS1 was upregulated in glioma tissues and cell lines, which was related to the grade of glioma and patient survival. Next, through functional assays, we found that COX10-AS1 influenced the proliferation, migration and invasion of glioma cell lines. Then, with the help of bioinformatics analysis, we confirmed that COX10-AS1 regulated glioma progress by acting as a sponge of miR-641 to regulate E2F6. Moreover, further study indicated that E2F6 could promote COX10-AS1 expression by binding to its promoter region. Taken together, the data indicated that COX10-AS1 acts as an oncogene in combination with COX10-AS1/miR-641/E2F6 in glioma, which may be beneficial to the diagnosis and treatment of glioma.

scholarly journals MicroRNA-92a Inhibits the Cell Viability and Metastasis of Prostate Cancer by Targeting SOX4

2020 ◽  
Vol 19 ◽  
pp. 153303382095935 ◽  
Author(s):  
Guolong Liao ◽  
Haiyun Xiong ◽  
Jiani Tang ◽  
Yamei Li ◽  
Ying Liu
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Biological Function ◽  
Active Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Biological Functions ◽  
Inhibitory Effects ◽  
Treatment Target ◽  
Complementary Sequences

MicroRNAs (miRNAs) was confirmed to play an active role in the pathogenesis of prostate cancer (PCa). The expression and biological function for miR-92a in PCa remains unknown. In this study, we demonstrated that miR-92a expression was decreased in PCa tissues and cells lines. Overexpression miR-92a inhibited the cell viability, migration and invasion of PC-3 while inhibition of miR-92a led to opposite alteration of cell viability and metastasis of DU-145 cells. Mechanically, we confirmed that miR-92a interacted with 3’-UTR of SOX4 through the complementary sequences by luciferase reporter assay. qRT-PCR and western blot confirmed that miR-92a inhibited the expression of SOX4 in PCa cells. Moreover, overexpression of SOX4 reversed the inhibitory effects of miR-92a overexpression on PC-3 cell viability, migration and invasion, while knockdown of SOX4 suppressed the promoting effects of miR-92a knockdown on these biological functions of DU-145 cells. Therefore, our study indicates that miR-92a inhibits the growth and metastasis of prostate cancer by targeting SOX4, and can potentially serve as a biomarker and treatment target for PCa patients.

scholarly journals Activation of the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B axis facilitates prostate cancer progression

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Chen Du ◽  
Caihong Lv ◽  
Yue Feng ◽  
Siwen Yu
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion

Abstract Background Accumulating evidence supports that lysine-specific demethylase 5 (KDM5) family members act as oncogenic drivers. This study was performed to elucidate the potential effects of KDM5A on prostate cancer (PCa) progression via the miR-495/YTHDF2/m6A-MOB3B axis. Methods The expression of KDM5A, miR-495, YTHDF2 and MOB3B was validated in human PCa tissues and cell lines. Ectopic expression and knockdown experiments were developed in PCa cells to evaluate their effects on PCa cell proliferation, migration, invasion and apoptosis. Mechanistic insights into the interaction among KDM5A, miR-495, YTHDF2 and MOB3B were obtained after dual luciferase reporter, ChIP, and PAR-CLIP assays. Me-RIP assay was used to determine m6A modification level of MOB3B mRNA in PCa cells. Mouse xenograft models of PCa cells were also established to monitor the tumor growth. Results KDM5A was highly expressed in human PCa tissues and cell lines. Upregulated KDM5A stimulated PCa cell proliferation, migration and invasion, but reduced cell apoptosis. Mechanistically, KDM5A, as a H3K4me3 demethylase, bound to the miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. Furthermore, KDM5A was found to downregulate MOB3B expression, consequently augmenting PCa cell proliferation, migration and invasion in vitro and promoting tumor growth in vivo via the miR-495/YTHDF2 axis. Conclusion In summary, our study highlights the potential of histone demethylase KDM5A activity in enhancing PCa progression, and suggests KDM5A as a promising target for PCa treatment.

scholarly journals MiR-30e-5p inhibits the migration and invasion of nasopharyngeal carcinoma via regulating the expression of MTA1

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Weiqun Hu ◽  
Wenfeng Yao ◽  
Haolin Li ◽  
Li Chen
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Western Blot ◽  
Cell Lines ◽  
Metastatic Cancer ◽  
Scratch Test ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Qrt Pcr ◽  
Related Proteins ◽  
The Relationship

Abstract The study explored the effect of miR-30e-5p on nasopharyngeal carcinoma (NPC). MiR-30e-5p levels in NPC cancer and adjacent normal samples, in metastatic and non-metastatic cancer samples of NPC, and in NP69 cell and five NPC cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between miR-30e-5p and MTA1 was confirmed by dual-luciferase reporter assay, Western blot and qRT-PCR. The viability, migration and invasion of 5-8F and 6-10B cells were determined by CCK-8, scratch test and transwell assays, respectively. The levels of migration-related proteins (vimentin and Snail) and invasion-related proteins (MMP2 and MMP3) in NPC cells were detected by Western blot. The results showed that low expression of miR-30e-5p was associated with HNSC cancer, NPC, metastasis of NPC and NPC cell lines. Overexpressed miR-30e-5p in HNSC cancer and NPC was predictive of a better prognosis of patients. In addition, the viability, migration and invasion were reduced by up-regulating miR-30e-5p in 5-8F cells, but promoted by down-regulated miR-30e-5p in 6-10B cells. MiR-30e-5p reversed the migration and invasion of NPC cells regulated by MTA1, and inhibited migration and invasion of NPC cells via regulating MTA1 expression.

scholarly journals The role of microRNA-572 in the proliferation and chemotherapeutic treatment of prostate cancer

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110143
Author(s):  
Mingcui Zang ◽  
Xun Guo ◽  
Manqiu Chen
Keyword(s):  
Prostate Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Prostate Tumorigenesis ◽  
Expression Levels ◽  
Matrigel Invasion ◽  
Tensin Homolog ◽  
Docetaxel Treatment ◽  
Induced Apoptosis

Objective MicroRNAs (miRNAs) regulate prostate tumorigenesis and progression by involving different molecular pathways. In this study, we examined the role of miR-572 in prostate cancer (PCa). Methods The proliferation rates of LNCaP and PC-3 PCa cells were studied using MTT assays. Transwell migration and Matrigel invasion assays were performed to evaluate cell migration and invasion, respectively. Protein expression levels were examined using western blotting. Docetaxel-induced apoptosis was evaluated by Caspase-Glo3/7 assays. The putative miR-572 binding site in the phosphatase and tensin homolog (PTEN) 3ʹ untranslated region (3ʹ UTR) was assessed with dual-luciferase reporter assays. Additionally, miR-572 expression levels in human PCa tissues were examined by qRT-PCR assays. Results Upregulation of miR-572 promoted proliferation, migration, and invasion of PCa cells. Overexpression of miR-572 decreased sensitivity of PCa cells to docetaxel treatment by reducing docetaxel-induced apoptosis. MiR-572 can regulate migration and invasion in PCa cells. Furthermore, miR-572 could regulate expression of PTEN and p-AKT in PCa cells by directly binding to the PTEN 3ʹ UTR. MiR-572 expression levels were increased in human PCa tissues and associated with PCa stage. Conclusions miR-572 displayed essential roles in PCa tumor growth and its expression level may be used to predict docetaxel treatment in these tumors.

scholarly journals Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caihong Wen ◽  
Xiaoqing Feng ◽  
Honggang Yuan ◽  
Yong Gong ◽  
Guangsheng Wang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Pdcd4 Expression ◽  
Novel Target

Abstract Background Circular RNAs (circRNAs) feature prominently in tumor progression. However, the biological function and molecular mechanism of circ_0003266 in colorectal cancer (CRC) require further investigation. Methods Circ_0003266 expression in 46 pairs CRC tissues / adjacent tissues, and CRC cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR); after circ_0003266 was overexpressed or knocked down in CRC cells, cell proliferation, apoptosis, migration, and invasion were evaluated by the cell counting kit-8 (CCK-8), flow cytometry, and Transwell assays, respectively; the interaction among circ_0003266, miR-503-5p, and programmed cell death 4 (PDCD4) was confirmed using bioinformatics analysis and dual-luciferase reporter assay; PDCD4 protein expression in CRC cells was quantified using Western blot. Results Circ_0003266 was significantly lowly expressed in CRC tissues and cell lines. Circ_0003266 overexpression markedly repressed CRC cell proliferation, migration, and invasion, and accelerated the cell apoptosis, but its overexpression promoted the malignant phenotypes of CRC cells. PDCD4 was a direct target of miR-503-5p and circ_0003266 promoted PDCD4 expression by competitively sponging miR-503-5p. Conclusion Circ_0003266 suppresses the CRC progression via sponging miR-503-5p and regulating PDCD4 expressions, which suggests that circ_0003266 may serve as a novel target for the treatment of CRC.

scholarly journals Long non-coding RNA CCDC183-AS1 acts AS a miR-589-5p sponge to promote the progression of hepatocellular carcinoma through regulating SKP1 expression

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
He Zhu ◽  
Hongwei Zhang ◽  
Youliang Pei ◽  
Zhibin Liao ◽  
Furong Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Human Cancer ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Regulatory Relationship

Abstract Background Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined. Methods Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1. Results Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC. Conclusions CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.

scholarly journals Acetyl-L-Carnitine downregulates invasion (CXCR4/CXCL12, MMP-9) and angiogenesis (VEGF, CXCL8) pathways in prostate cancer cells: rationale for prevention and interception strategies

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Denisa Baci ◽  
Antonino Bruno ◽  
Caterina Cascini ◽  
Matteo Gallazzi ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Dietary Supplements ◽  
Cell Lines ◽  
Angiogenic Factors ◽  
Migration And Invasion ◽  
Prostate Cancer Cells

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, representing valid compounds to target the aberrant cytokine/chemokine production governing PCa progression and angiogenesis, in a chemopreventive setting. Using mass spectrometry analysis on serum samples of prostate cancer patients, we have previously found higher levels of carnitines in non-cancer individuals, suggesting a protective role. Here we investigated the ability of Acetyl-L-carnitine (ALCAR) to interfere with key functional properties of prostate cancer progression and angiogenesis in vitro and in vivo and identified target molecules modulated by ALCAR. Methods The chemopreventive/angiopreventive activities ALCAR were investigated in vitro on four different prostate cancer (PCa) cell lines (PC-3, DU-145, LNCaP, 22Rv1) and a benign prostatic hyperplasia (BPH) cell line. The effects of ALCAR on the induction of apoptosis and cell cycle arrest were investigated by flow cytometry (FC). Functional analysis of cell adhesion, migration and invasion (Boyden chambers) were performed. ALCAR modulation of surface antigen receptor (chemokines) and intracellular cytokine production was assessed by FC. The release of pro-angiogenic factors was detected by a multiplex immunoassay. The effects of ALCAR on PCa cell growth in vivo was investigated using tumour xenografts. Results We found that ALCAR reduces cell proliferation, induces apoptosis, hinders the production of pro inflammatory cytokines (TNF-α and IFN-γ) and of chemokines CCL2, CXCL12 and receptor CXCR4 involved in the chemotactic axis and impairs the adhesion, migration and invasion capabilities of PCa and BPH cells in vitro. ALCAR exerts angiopreventive activities on PCa by reducing production/release of pro angiogenic factors (VEGF, CXCL8, CCL2, angiogenin) and metalloprotease MMP-9. Exposure of endothelial cells to conditioned media from PCa cells, pre-treated with ALCAR, inhibited the expression of CXCR4, CXCR1, CXCR2 and CCR2 compared to those from untreated cells. Oral administration (drinking water) of ALCAR to mice xenografted with two different PCa cell lines, resulted in reduced tumour cell growth in vivo. Conclusions Our results highlight the capability of ALCAR to down-modulate growth, adhesion, migration and invasion of prostate cancer cells, by reducing the production of several crucial chemokines, cytokines and MMP9. ALCAR is a widely diffused dietary supplements and our findings provide a rational for studying ALCAR as a possible molecule for chemoprevention approaches in subjects at high risk to develop prostate cancer. We propose ALCAR as a new possible “repurposed agent’ for cancer prevention and interception, similar to aspirin, metformin or beta-blockers.

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