lncRNA SNHG14 promotes the proliferation, migration, and invasion of thyroid tumour cells by regulating miR-93-5p

Summary Long non-coding RNAs (lncRNAs) exert vital functions in the occurrence and development of various tumours. The aim of this study was to examine the regulatory effect and underlying molecular mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) on the proliferation, invasion and migration of thyroid tumour cells. The expression of SNHG14 in thyroid tumour cell lines was determined using qRT-PCR. CCK-8 and western blot were used to detect the effects of SNHG14 on proliferation and apoptosis of thyroid tumour cells. The effect of SNHG14 on the migration and invasion of thyroid tumour cells was analyzed using immunofluorescence, wound-healing and transwell assays. A targeting relationship between SNHG14 and miR-93-5p was determined using bioinformatics software and luciferase reporter assays. In addition, CCK-8, immunofluorescence, wound-healing and transwell assays were applied to demonstrate that SNHG14 promoted the proliferation, migration and invasion of thyroid tumour cells by targeting miR-93-5p. The biological function of SNHG14 in vivo was explored through a xenograft model and immunohistochemistry. SNHG14 was upregulated in thyroid tumour cells compared with normal cells. Downregulation of SNHG14 effectively reduced the proliferation, migration and invasion of TPC-1 cells, and induced cell apoptosis. Moreover, SNHG14 directly targeted miR-93-5p and there was a negative correlation between them. Further functional experiments illustrated that miR-93-5p overexpression dramatically reversed the promoting role of SNHG14 in proliferation, migration and invasion of TPC-1 cells. Our results demonstrated that SNHG14 promotes the proliferation, invasion and migration of thyroid tumour cells by downregulating miR-93-5p.

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MiR-134, Mediated by IRF1, Suppresses Tumorigenesis and Progression by Targeting VEGFA and MYCN in Osteosarcoma

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200402074752 ◽

2020 ◽

Vol 20 (10) ◽

pp. 1197-1208

Author(s):

Zhuo Ma ◽

Kai Li ◽

Peng Chen ◽

Qizheng Pan ◽

Xuyang Li ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Mrna Levels ◽

Invasion And Migration ◽

And Migration

Background: Osteosarcoma (OS) is a prevalent primary bone malignancy and its distal metastasis remains the main cause of mortality in OS patients. MicroRNAs (miRNAs) play critical roles during cancer metastasis. Objective: Thus, elucidating the role of miRNA dysregulation in OS metastasis may provide novel therapeutic targets. Methods: The previous study found a low miR-134 expression level in the OS specimens compared with paracancer tissues. Overexpression of miR-134 stable cell lines was established. Cell viability assay, cell invasion and migration assay and apoptosis assay were performed to evaluate the role of miR-134 in OS in vitro. Results: We found that miR-134 overexpression inhibits cell proliferation, migration and invasion, and induces cell apoptosis in both MG63 and Saos-2 cell lines. Mechanistically, miR-134 targets the 3'-UTR of VEGFA and MYCN mRNA to silence its translation, which was confirmed by luciferase-reporter assay. The real-time PCR analysis illustrated that miR-134 overexpression decreases VEGFA and MYCN mRNA levels. Additionally, the overexpression of VEGFA or MYCN can partly attenuate the effects of miR-134 on OS cell migration and viability. Furthermore, the overexpression of miR-134 dramatically inhibits tumor growth in the human OS cell line xenograft mouse model in vivo. Moreover, bioinformatic and luciferase assays indicate that the expression of miR-134 is regulated by Interferon Regulatory Factor (IRF1), which binds to its promoter and activates miR-134 expression. Conclusion: Our study demonstrates that IRF1 is a key player in the transcriptional control of miR-134, and it inhibits cell proliferation, invasion and migration in vitro and in vivo via targeting VEGFA and MYCN.

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Hsa_circ_0001944 promotes the growth and metastasis in bladder cancer cells by acting as a competitive endogenous RNA for miR-548

10.21203/rs.3.rs-44045/v3 ◽

2020 ◽

Author(s):

Mingming Jin ◽

Shengjie Lu ◽

Yue Wu ◽

Chen Yang ◽

Chunzi Shi ◽

...

Keyword(s):

Bladder Cancer ◽

High Throughput Sequencing ◽

Expression Profiles ◽

Xenograft Model ◽

Luciferase Reporter ◽

Circular Rnas ◽

Invasion And Migration ◽

And Migration

Abstract Background: Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in cancer development, including BC; thus, the roles of circRNAs in this process have attracted significant attention. Methods: In this study, high-throughput sequencing was used to analyze circRNA expression profiles in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression in BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor cell proliferation, invasion, and migration, respectively. We employed the dual-luciferase reporter and RNA pulldown assays to verify the relationships among hsa_circ_0001944, miR-548, and PROK2. We examined the effects of hsa_circ_0001944 on BC cell metastasis and proliferation in vivo using a subcutaneous xenograft model and an intravenous tail injection model in nude mice. Results: The results showed that hsa_circ_0001944 expression was significantly increased in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. Conclusions: Taken together, we found that hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions as a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.

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Hsa_circ_0001944 promotes the growth and metastasis in bladder cancer cells by acting as a competitive endogenous RNA for miR-548

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01697-6 ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Mingming Jin ◽

Shengjie Lu ◽

Yue Wu ◽

Chen Yang ◽

Chunzi Shi ◽

...

Keyword(s):

Bladder Cancer ◽

High Throughput Sequencing ◽

Expression Profiles ◽

Xenograft Model ◽

Luciferase Reporter ◽

Circular Rnas ◽

Invasion And Migration ◽

And Migration

Abstract Background Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in cancer development, including BC; thus, the roles of circRNAs in this process have attracted significant attention. Methods In this study, high-throughput sequencing was used to analyze circRNA expression profiles in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression in BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor cell proliferation, invasion, and migration, respectively. We employed the dual-luciferase reporter and RNA pulldown assays to verify the relationships among hsa_circ_0001944, miR-548, and PROK2. We examined the effects of hsa_circ_0001944 on BC cell metastasis and proliferation in vivo using a subcutaneous xenograft model and an intravenous tail injection model in nude mice. Results The results showed that hsa_circ_0001944 expression was significantly increased in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. Conclusions Taken together, we found that hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions as a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.

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Decreased hsa_circ_0001944 expression is associated with improved bladder cancer prognoses

10.21203/rs.3.rs-44045/v2 ◽

2020 ◽

Author(s):

Mingming Jin ◽

Shengjie Lu ◽

Yue Wu ◽

Chen Yang ◽

Chunzi Shi ◽

...

Keyword(s):

Bladder Cancer ◽

High Throughput Sequencing ◽

Expression Profiles ◽

Xenograft Model ◽

Luciferase Reporter ◽

Circular Rnas ◽

Invasion And Migration ◽

And Migration

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Hispidulin inhibits proliferation, migration, and invasion by promoting autophagy via regulation of PPARγ activation in prostate cancer cells and xenograft models

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa108 ◽

2020 ◽

Author(s):

Yuanyuan Wang ◽

Shanqi Guo ◽

Yingjie Jia ◽

Xiaoyu Yu ◽

Ruiyu Mou ◽

...

Keyword(s):

Prostate Cancer ◽

Flavonoid Compound ◽

Migration And Invasion ◽

Prostate Cancer Cells ◽

Invasion And Migration ◽

Beneficial Effects ◽

Anticancer Properties ◽

Xenograft Models ◽

And Migration

ABSTRACT Prostate cancer (PCa) is one of the important factors of cancer deaths especially in the western countries. Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid compound proved to possess anticancer properties, but its effects on PCa are left to be released. The aims of this study were to investigate the effects and the relative mechanisms of Hispidulin on PCa development. Hispidulin administration inhibited proliferation, invasion, and migration, while accelerated apoptosis in Du145 and VCaP cells, which was accompanied by PPARγ activation and autophagy enhancement. The beneficial effects of Hispidulin could be diminished by PPARγ inhibition. Besides, Hispidulin administration suppressed PCa tumorigenicity in Xenograft models, indicating the anticancer properties in vivo. Therefore, our work revealed that the anticancer properties of Hispidulin might be conferred by its activation on PPARγ and autophagy.

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Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02274-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Qingjuan Meng ◽

Ningning Wang ◽

Guanglan Duan

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Invasion And Migration ◽

Non Coding Rna ◽

And Migration ◽

Long Non Coding Rna

Abstract Background X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. Methods RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. Results The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. Conclusion XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.

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MiR-196b Promotes the Invasion and Migration of Lung Adenocarcinoma Cells by Targeting AQP4

Technology in Cancer Research & Treatment ◽

10.1177/1533033820985868 ◽

2021 ◽

Vol 20 ◽

pp. 153303382098586

Author(s):

Xuhui Wu ◽

Gongzhi Wu ◽

Huaizhong Zhang ◽

Xuyang Peng ◽

Bin Huang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Cell Invasion ◽

Target Gene ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Reporter Assay ◽

Invasion And Migration ◽

And Migration ◽

Dual Luciferase Reporter Assay

Objective: We aimed to investigate the mechanism of the regulatory axis of miR-196b/AQP4 underlying the invasion and migration of lung adenocarcinoma (LUAD) cells. Methods: LUAD miRNA and mRNA expression profiles were downloaded from TCGA database and then differential analysis was used to identify the target miRNA. Target gene for the miRNA was obtained via prediction using 3 bioinformatics databases and intersection with the differentially expressed mRNAs searched from TCGA-LUAD. Then, qRT-PCR and western blot were used to validate the expression of miR-196b and AQP4. Dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-196b and AQP4. Transwell assay was used to investigate the migration and invasion of LUAD cells. Results: MiR-196b was screened out by differential and survival analyses, and the downstream target gene AQP4 was identified. In LUAD, miR-196b was highly expressed while AQP4 was poorly expressed. Besides, overexpression of miR-196b promoted cell invasion and migration, while overexpression of AQP4 had negative effects. Moreover, the results of the dual-luciferase reporter assay suggested that AQP4 was a direct target of miR-196b. In addition, we also found that overexpressing AQP4 could suppress the promotive effect of miR-196b on cancer cell invasion and migration. Conclusion: MiR-196b promotes the invasion and migration of LUAD cells by down-regulating AQP4, which helps us find new molecular targeted therapies for LUAD.

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The transcription factor USF1 promotes glioma cell invasion and migration by activating lncRNA HAS2-AS1

Bioscience Reports ◽

10.1042/bsr20200487 ◽

2020 ◽

Vol 40 (8) ◽

Author(s):

Juntong Wang ◽

Jingshun Gu ◽

Aiwu You ◽

Jun Li ◽

Yuyan Zhang ◽

...

Keyword(s):

Transcription Factor ◽

Cell Invasion ◽

Promoter Region ◽

Glioma Cell ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Starting Point ◽

And Migration

Abstract Objective: The role of lncRNAs in tumor has been widely concerned. The present study took HAS2-AS1 (the antisense RNA 1 of HAS2) as a starting point to explore its expression in glioma and its role in the process of migration and invasion, providing a strong theoretical basis for mining potential therapeutic targets of glioma. Methods: Clinical data of glioma were obtained from The Cancer Genome Atlas (TCGA) database and differentially expressed lncRNAs were analyzed by edgeR. The hTFtarget database was used to predict the upstream transcription factors of HAS2-AS1 and the JASPAR website was used to predict the binding sites of human upstream transcription factor 1 (USF1) and HAS2-AS1. qRT-PCR was used to detect the expressions of HAS2-AS1 and USF1 in glioma tissues and cell lines. The effects of silencing HAS2-AS1 on the migration and invasion of cancer cells were verified by wound healing and Transwell invasion assays. The chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were applied to demonstrate the binding of USF1 and HAS2-AS1 promoter region. Western blot was used to detect the expressions of epithelial–mesenchymal transition (EMT)-related proteins. Results: HAS2-AS1 was highly expressed in glioma tissues and cells, and was significantly associated with poor prognosis. Silencing HAS2-AS1 expression inhibited glioma cell migration, invasion and EMT. USF1 was highly expressed in glioma and positively correlated with HAS2-AS1. The transcription of HAS2-AS1 was activated by USF1 via binding to HAS2-AS1 promoter region, consequently potentiating the invasion and migration abilities of glioma cells. Conclusion: These results suggested that the transcription factor USF1 induced up-regulation of lncRNA HAS2-AS1 and promoted glioma cell invasion and migration.

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MiR-125b-5p Inhibited The Progression of Hepatoblastoma As A Shared miRNA of The lncRNA NEAT1 and YES1

10.21203/rs.3.rs-49445/v1 ◽

2020 ◽

Author(s):

Zhu Jin ◽

Yutong Chen ◽

Yuchen Mao ◽

Mingjuan Gao ◽

Zebing Zheng ◽

...

Keyword(s):

Clinicopathological Characteristics ◽

Luciferase Reporter ◽

Tumor Growth Inhibition ◽

Invasion And Migration ◽

In Vivo Experiments ◽

Reporter Assays ◽

And Migration ◽

Relationship Of

Abstract Background: microRNAs have been studied widely in hepatoblastoma. However, the role of miR-125b-5p and its relationship with the lncRNA sNEAT1 and YES1 in hepatoblastoma have not been reported previously. We aimed to reveal the role of NEAT1/miR-125b-5p/YES1 in the progression of hepatoblastoma.Methods: We collected tumor tissues and their adjacent tissues from 12 hepatoblastoma patients. qRT-PCR was applied to detect the expression of miR-125b-5p, and the relationship of miR-125b-5p with clinicopathological characteristics was analyzed. Dual luciferase reporter assays and RNA pull down assays were used to identify the relationships among NEAT1, miR-125b-5p and YES1. CCK8, Transwell assays and wound healing assays were used to examine cell viability, invasion and migration. In vivo experiments were also applied to detect the effect of miR-125b-5p on hepatoblastoma.Results: miR-125b-5p was significantly downregulated in hepatoblastoma tissue and cells. The higher the PRETEXT grade, the lower the miR-125b-5p level. NEAT1 could bind to miR-125b-5p and inhibit its expression. miR-125b-5p could target YES1 and inhibit its expression. Overexpression of miR-125b-5p decreased the proliferation, invasion, and migratory ability of hepatoblastoma cells. YES1 could rescue the above effects. At the same time, overexpression of miR-125b-5p resulted in decreased YES1 and tumor growth inhibition in vivo.Conclusion: miR-125b-5p acted as a shared miRNA of NEAT1 and YES1 in hepatoblastoma. Overexpression of miR-125b-5p could target YES1 and inhibit its expression, therefore inhibiting the progression of hepatoblastoma.

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MiR-92a-3p promote s invasion and migration of hepatocellular carcinoma cells by targeting PTEN

10.21203/rs.3.rs-408247/v1 ◽

2021 ◽

Author(s):

Yilin Hu ◽

Huiling Sun ◽

Qiping Lu ◽

Hongliang Mei ◽

Rong Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Mutation Frequency ◽

Biological Information ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Clinical Samples ◽

Luciferase Reporter Gene ◽

Invasion And Migration ◽

And Migration ◽

The Impact

Abstract Background MiR-92a-3p has been reported to play a part in hepatocellular carcinoma (HCC), a leading type of lethal cancer around the world. In this study, we explored the function and mechanism of miR-92a-3p in HCC. Methods Firstly, the expression of miR-92a-3p in HCC along with its relationship with PTEN was analyzed through biological information. To investigate the impact of miR-92a-3p on the migration and invasion of HCC cells, we performed scratch wound healing and transwell assays. Next, RT-qPCR, western blot and dual luciferase reporter gene assays were conducted to determine whether PTEN is targeted by miR-92a-3p, which was then verified through rescue assays. Afterwards, in vivo animal experiments were carried out to determine the function of miR-92a-3p in HCC tissues. As an established fact, PETN is an anti-oncogene with frequent mutation inactivation in human cancers. Thus, we used the database to predict the mutation of PETN and its mutation frequency. Finally, CRISPR-cas12a was applied to detect the R130Q mutation on PETN in HCC clinical samples. Results This study found that the migration and invasion of HCC could be suppressed by inhibiting miR-92a-3p, which regulates the proliferation, migration and invasion of HCC through the regulation of PETN. The bioinformatics analysis indicated higher mutation frequency of R130Q/G/L* site on the PETN gene, and greater impact of R130Q site mutation on the progression of HCC. CRISPR-cas12a detected 26 cases of R130Q mutations on PTEN in 40 HCC clinical samples Conclusion Collectively, this study revealed that miR-92a-3p promoted the invasion and migration of HCC by targeting PTEN, and that the stability of PETN also affected the development of HCC, which may enrich and deepen our knowledge on the progression of HCC.

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