The TWIST1-centered competing endogenous RNA network promotes proliferation, invasion, and migration of lung adenocarcinoma

Abstract The proposed competing endogenous RNA (ceRNA) mechanism suggested that diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs could communicate with each other by competing for binding to shared microRNAs. The ceRNA network (ceRNET) is involved in tumor progression and has become a hot research topic in recent years. To date, more attention has been paid to the role of non-coding RNAs in ceRNA crosstalk. However, coding transcripts are more abundant and powerful than non-coding RNAs and make up the majority of miRNA targets. In this study, we constructed a mRNA-mRNA related ceRNET of lung adenocarcinoma (LUAD) and identified the highlighted TWIST1-centered ceRNET, which recruits SLC12A5 and ZFHX4 as its ceRNAs. We found that TWIST1/SLC12A5/ZFHX4 are all upregulated in LUAD and are associated with poorer prognosis. SLC12A5 and ZFHX4 facilitated proliferation, migration, and invasion in vivo and in vitro, and their effects were reversed by miR-194–3p and miR-514a-3p, respectively. We further verified that SLC12A5 and ZFHX4 affected the function of TWIST1 by acting as ceRNAs. In summary, we constructed a mRNA-mRNA related ceRNET for LUAD and highlighted the well-known oncogene TWIST1. Then we verified that SLC12A5 and ZFHX4 exert their oncogenic function by regulating TWIST1 expression through a ceRNA mechanism.

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CircGSK3B promotes RORA expression and suppresses gastric cancer progression through the prevention of EZH2 trans-inhibition

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02136-w ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Xianxiong Ma ◽

Hengyu Chen ◽

Lei Li ◽

Feng Yang ◽

Chuanqing Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Gene Expression Regulation ◽

Migration And Invasion ◽

Circular Rnas ◽

Loss Of Function ◽

Invasion And Migration ◽

And Migration

Abstract Background Circular RNAs (circRNAs) are a class of non-coding RNA that play critical roles in the development and pathogenesis of various cancers. The circRNA circGSK3B (hsa_circ_0003763) has been shown to enhance cell proliferation, migration, and invasion in hepatocellular carcinoma. However, the specific functions and underlying mechanistic involvement of circGSK3B in gastric cancer (GC) have not yet been explored. Our study aimed to investigate the effect of circGSK3B on the progression of GC and to identify any potential mechanisms underlying this process. Methods CircRNA datasets associated with GC were obtained from the PubMed, GEO, and ArrayExpress databases, and circRNAs were validated via RT-qPCR and Sanger sequencing. Biotin-labeled RNA pull-down, mass spectrometry, RNA immunoprecipitation, and in vitro binding assays were employed to determine proteins demonstrating interactions with circGSK3B. Gene expression regulation was assessed through RT-qPCR, chromatin immunoprecipitation, and western blot assays. Gain- and loss-of-function assays were used to analyze any effects of circGSK3B and its partner regulatory molecule (EZH2) on the proliferation, invasion, and migration abilities of GC cells both in vitro and in vivo. Results CircGSK3B was mainly identified in the nucleus. This circRNA was present at a reduced concentration in GC tissues and cell lines. Overexpression of circGSK3B was shown to inhibit the growth, invasion, and metastasis of GC cells both in vitro and in vivo. Mechanistically, circGSK3B directly interacted with EZH2, acting to suppress the binding of EZH2 and H3K27me3 to the RORA promoter, and leading to an elevation in RORA expression and ultimately the suppression of GC progression. Conclusions CircGSK3B acts as a tumor suppressor, reducing EZH2 trans-inhibition and GC progression. This demonstrates the potential use of this RNA as a therapeutic target for GC.

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Circular METRN RNA hsa_circ_0037251 Promotes Glioma Progression by Sponging miR-1229-3p and Regulating mTOR Expression

Scientific Reports ◽

10.1038/s41598-019-56417-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Qinchen Cao ◽

Yonggang Shi ◽

Xinxin Wang ◽

Jing Yang ◽

Yin Mi ◽

...

Keyword(s):

Glioma Cell ◽

High Expression ◽

Circular Rnas ◽

Invasion And Migration ◽

Cellular Processes ◽

Cell Progression ◽

And Migration ◽

Glioma Progression

AbstractCircular RNAs (circRNAs) are a newly identifed non-coding RNA in many cellular processes and tumours. This study aimed to investigate the role of hsa_circ_0037251, one circRNA generated from several exons of the gene termed METRN, in glioma progression. Through in vitro experiments, we discovered that high expression of hsa_circ_0037251 was related to low expression of the microRNA miR-1229-3p and high expression of mTOR. The over-expressed hsa_circ_0037251 promoted cell proliferation, invasion and migration in glioma, while knockdown of hsa_circ_00037251 promoted cell apoptosis and induced G1 phase arrest. Then, hsa_circ_0037251 was observed to directly sponge miR-1229-3p, and mTOR was identified as a direct target of miR-1229-3p. In addition, knockdown of hsa_circ_0037251 up-regulated the expression of miR-1229-3p and inhibited the expression of mTOR. And overexpression of miR-1229-3p or low-expressed mTOR inhibited the glioma cell progression. Furthermore, transfection with mTOR overexpression vectors can restore the abilities of glioma cell progression even if hsa_circ_00037251 was knocked down using siRNAs. In vivo experiments revealed that hsa_circ_00037251 promoted the growth of xenografted tumours and shortened the survival period. These results indicated that hsa_circ_0037251 may act as a tumour promoter by a hsa_circ_0037251/miR-1229-3p/mTOR axis, and these potential biomarkers may be therapeutic targets for glioma.

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CHD5 inhibits metastasis of neuroblastoma

Oncogene ◽

10.1038/s41388-021-02081-0 ◽

2021 ◽

Author(s):

Astrid K. Laut ◽

Carmen Dorneburg ◽

Axel Fürstberger ◽

Thomas F. E. Barth ◽

Hans A. Kestler ◽

...

Keyword(s):

Migration And Invasion ◽

Metastasis Suppressor ◽

Invasion And Migration ◽

Gene Sets ◽

Genome Wide ◽

And Migration ◽

Key Aspects ◽

Low Expression

AbstractCHD5, a tumor suppressor at 1p36, is frequently lost or silenced in poor prognosis neuroblastoma (NB) and many adult cancers. The role of CHD5 in metastasis is unknown. We confirm that low expression of CHD5 is associated with stage 4 NB. Forced expression of CHD5 in NB cell lines with 1p loss inhibited key aspects of the metastatic cascade in vitro: anchorage-independent growth, migration, and invasion. In vivo, formation of bone marrow and liver metastases developing from intravenously injected NB cells was delayed and decreased by forced CHD5 expression. Genome-wide mRNA sequencing revealed reduction of genes and gene sets associated with metastasis when CHD5 was overexpressed. Known metastasis-suppressing genes preferentially upregulated in CHD5-overexpressing NB cells included PLCL1. In patient NB, low expression of PLCL1was associated with metastatic disease and poor survival. Knockdown of PLCL1 and of p53 in IMR5 NB cells overexpressing CHD5 reversed CHD5-induced inhibition of invasion and migration in vitro. In summary, CHD5 is a metastasis suppressor in NB.

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LncRNA SNHG20 promotes migration and invasion of ovarian cancer via modulating the microRNA-148a/ROCK1 axis

Journal of Ovarian Research ◽

10.1186/s13048-021-00889-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Qi Yang ◽

Yu-Jie Dong

Keyword(s):

Ovarian Cancer ◽

Cell Lines ◽

Noncoding Rna ◽

Tumor Xenograft ◽

Migration And Invasion ◽

Epithelial Cell Line ◽

Invasion And Migration ◽

And Migration

Abstract Background Ovarian cancer (OC) is characterized by early metastasis and poor prognosis, which threatens the health of women worldwide. Small nucleolar RNA host gene 20 (SNHG20), a long noncoding RNA (lncRNA), has been verified to be significantly up-regulated in several tumors, including OC. MicroRNA-148a (miR-148a)/rho-kinase1 (ROCK1) axis plays an important role in the modulation of tumor development. However, whether SNHG20 can regulate OC progression through miR-148a/ROCK1 axis remains unclear. Normal human ovarian epithelial cell line and four OC cell lines were adopted for in vitro experiments. Real-time PCR was performed to assess the levels of SNHG20 and miR-148a. OC cell proliferation, apoptosis, invasion and migration were detected using clone formation, flow cytometry, transwell, and wound healing assays, respectively. Tumor xenograft assay was applied to evaluate the effect of SNHG20 on tumor growth in vivo. Results Significant higher expression of SNHG20 was observed in OC cell lines. SNHG20 markedly promoted the invasion, migration, proliferation and inhibited the apoptosis of OC cells. SNHG20 enhanced ROCK1 expression by sponging miR-148a, and the direct binding between SNHG20/ROCK1 and miR-148a was identified. Conclusion SNHG20 promoted invasion and migration of OC via targeting miR-148a/ROCK1 axis. The present research may provide a novel insight for the therapeutic strategies of OC.

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Long non-coding RNA CASC15 promotes HCC progression via modulation of Six1 targeted by miR-2355-5p

10.21203/rs.3.rs-27428/v1 ◽

2020 ◽

Author(s):

Han Hong ◽

Chengjun Sui ◽

Tao Qian ◽

Xiaoyong Xu ◽

Xiang Zhu ◽

...

Keyword(s):

Expression Level ◽

Migration And Invasion ◽

Expression Levels ◽

Invasion And Migration ◽

Downstream Target ◽

Non Coding Rna ◽

And Migration ◽

Hcc Cells

Abstract Background: Long-chain non-coding RNA (LncRNA) plays a key role in the biological processes of tumors. LncRNA CASC15 has been shown to be involved in the development of a variety of tumors. The study aimed to elucidate the mechanism of lncRNA CASC15 in the progression of hepatocellular carcinomas (HCC).Methods: qRT-PCR was used to detect the expression levels of CASC15, miR-2355-5p and Six1 mRNA in HCC tissues and cells. Six1 protein expression levels were detected by Western Blot. CCK-8 experiment, colony formation experiment, Edu staining and Transwell experiment analysis were used to analyze the effects of CASC15, miR-2355-5p and Six1 on cell proliferation, cell invasion and migration. The relationship between CASC15, miR-2355-5p and Six1 was analyzed using bioinformatics analysis and Luciferase.Result: CASC15 was raised in HCC tissues and HCC cells. Down-regulation of CASC15 inhibited the growth, migration, invasion and tumor growth of HCC cells. The expression level of miR-2355-5p was reduced in HCC tissues. In addition, miR-2355-5p inhibitor induced the growth, migration and invasion of HCC cells. MiR-2355-5p was predicted to be a downstream target of CASC15. The expression level of miR-2355-5p was negatively correlated with CASC15 in HCC tumor tissues. Six1 was predicted to be a downstream target of miR-30a-5p. In vitro and in vivo results showed that CASC15/miR-2355-5p can regulate Six1.Conclusion: LncCASC15 regulated the proliferation and invasion of Six1 by binding with miR-2355-5p in HCC, suggesting that CASC15 may be a potential target for HCC.

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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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C/EBPα Suppresses Lung Adenocarcinoma Cell Invasion and Migration by Inhibiting β-Catenin

Cellular Physiology and Biochemistry ◽

10.1159/000479457 ◽

2017 ◽

Vol 42 (5) ◽

pp. 1779-1788 ◽

Cited By ~ 6

Author(s):

Jinchang Lu ◽

Chunling Du ◽

Junxia Yao ◽

Bo Wu ◽

Yanhong Duan ◽

...

Keyword(s):

Transcription Factor ◽

Lung Adenocarcinoma ◽

Cell Invasion ◽

Migration And Invasion ◽

Adenocarcinoma Cell ◽

Invasion And Migration ◽

Adenocarcinoma Cells ◽

Lung Adenocarcinoma Cells ◽

And Migration

Background/Aims: The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) is a basic leucine zipper transcription factor that plays essential roles in tumor progression. Although decreased or absent C/EBPα expression in many cancers suggests a possible role for C/EBPα as a tumor suppressor, the functions of C/EBPα in lung adenocarcinoma remain unclear. Methods: Here, C/EBPα expression levels in 26 lung adenocarcinoma and para-carcinoma tissue samples were detected by qRT-PCR and immunohistochemistry. Cell transwell assays, wound healing assay and three-dimensional spheroid invasion assay were performed to assess the effects of C/EBPα on migration and invasion in lung adenocarcinoma cells in vitro. Western blotting was applied to analyze the potential mechanisms. Results: C/EBPα was found to be decreased in lung adenocarcinoma tissues compared to para-carcinoma tissues. Overexpression of C/EBPα significantly inhibited the migration and invasion of lung adenocarcinoma cells. In addition, C/EBPα overexpression suppressed the epithelial–mesenchymal transition (EMT) that was characterized by a gain of epithelial and loss of mesenchymal markers. Further study showed that C/EBPα suppressed the transcription of β-catenin and downregulated the levels of its downstream targets. Conclusion: Our data suggest that C/EBPα inhibits lung adenocarcinoma cell invasion and migration by suppressing β-catenin-mediated EMT in vitro. Thus, C/EBPα may be helpful as a potential target for treatment of lung adenocarcinoma.

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The Interaction Between Long Non-Coding RNA LINC01564 and POU2F1 Promotes the Proliferation and Metastasis of Gastric Cancer

10.21203/rs.3.rs-914479/v1 ◽

2021 ◽

Author(s):

Jixu Wang ◽

Futao Hou ◽

Lusheng Tang ◽

Ke Xiao ◽

Tengfei Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Transcription Factor ◽

Tumor Development ◽

Transcription Activation ◽

Migration And Invasion ◽

Invasion And Migration ◽

Proliferation And Metastasis ◽

And Migration

Abstract Background: An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) serve as key regulators in tumor development and progression. However, only a few lncRNAs have been functionally characterized in gastric cancer (GC). Methods: Bioinformatics analysis was conducted to find lncRNAs that are associated with GC metastasis. RNA FISH, RIP, and RNA pull down assays were used to study the complementary binding of LINC01564 complementary to the 3’UTR of transcription factor POU2F1. The transcription activation of LINC01564 by POU2F1 as a transcription factor was examined by ChIP assay. In vitro assays such as MTT, cell invasion assay, and clonogenic assay were conducted to examined the impacts of LINC01564 and POU2F1 on GC cell proliferation and invasion. Experiments in vivo were performed to access the impacts of LINC01564 and POU2F1 on GC metastasis. Results: The results showed that LINC01564 complementary bound to the 3’UTR of POU2F1 to form an RNA duplex, whereby stabilizing POU2F1 mRNA and increasing the enrichment in cells. The level of LINC01564 was also increased by POU2F1 through transcription activation. In vitro assays showed that LINC01564 promoted the proliferation, invasion and migration of GC cells through increasing POU2F1. In vivo experiments indicate the promotion of GC proliferation and metastasis by the interaction between LINC01564 and POU2F1. Conclusion: Taken together, our results indicate that the interaction between LINC01564 and POU2F1 promotes the proliferation, migration and invasion of GC cells.

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Lnc-RNA CASC15 promotes HCC progression via modulation of Six1 targeted by miR-2355-5p

10.21203/rs.3.rs-27428/v2 ◽

2020 ◽

Author(s):

Han Hong ◽

Chengjun Sui ◽

Tao Qian ◽

Xiaoyong Xu ◽

Xiang Zhu ◽

...

Keyword(s):

Expression Level ◽

Migration And Invasion ◽

Expression Levels ◽

Invasion And Migration ◽

Downstream Target ◽

Non Coding Rna ◽

And Migration ◽

Hcc Cells

Abstract Background: Long-chain non-coding RNA (LncRNA) plays a key role in the biological processes of tumors. LncRNA CASC15 has been shown to be involved in the development of a variety of tumors. The study aimed to elucidate the mechanism of lncRNA CASC15 in the progression of hepatocellular carcinomas (HCC). Methods: qRT-PCR was used to detect the expression levels of CASC15, miR-2355-5p and Six1 mRNA in HCC tissues and cells. Six1 protein expression levels were detected by Western Blot. CCK-8 experiment, colony formation experiment, Edu staining and Transwell experiment analysis were used to analyze the effects of CASC15, miR-2355-5p and Six1 on cell proliferation, cell invasion and migration. The relationship between CASC15, miR-2355-5p and Six1 was analyzed using bioinformatics analysis and Luciferase. Result: CASC15 was raised in HCC tissues and HCC cells. Down-regulation of CASC15 inhibited the growth, migration, invasion and tumor growth of HCC cells. The expression level of miR-2355-5p was reduced in HCC tissues. In addition, miR-2355-5p inhibitor induced the growth, migration and invasion of HCC cells. MiR-2355-5p was predicted to be a downstream target of CASC15. The expression level of miR-2355-5p was negatively correlated with CASC15 in HCC tumor tissues. Six1 was predicted to be a downstream target of miR-30a-5p. In vitro and in vivo results showed that CASC15/miR-2355-5p can regulate Six1.Conclusion: LncCASC15 regulated the proliferation and invasion of Six1 by binding with miR-2355-5p in HCC, suggesting that CASC15 may be a potential target for HCC.

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Novel cytoplasmic lncRNA IKBKBAS promotes lung adenocarcinoma metastasis by upregulating IKKβ and consequential activation of NF-κB signaling pathway

Cell Death and Disease ◽

10.1038/s41419-021-04304-4 ◽

2021 ◽

Vol 12 (11) ◽

Author(s):

Yuanxin Xing ◽

Yani Lin ◽

Ying Zhang ◽

Jing Hu ◽

Junmei Liu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Signaling Pathway ◽

Feedback Loop ◽

Competing Endogenous Rna ◽

Positive Feedback Loop ◽

Non Coding Rnas ◽

Novel Target ◽

Critical Link

AbstractNF-κB signaling pathway is a critical link between inflammation and cancer. Emerging evidence suggested that long non-coding RNAs (lncRNAs) were involved in dysregulation of NF-κB. Herein, we reported a novel lncRNA IKBKBAS that activated NF-κB in lung adenocarcinoma (LUAD) by upregulating IKKβ, a key member of NF-κB signaling pathway, thereby promoting the metastasis of LUAD both in vitro and in vivo. The upregulated IKBKBAS functioned as a competing endogenous RNA (ceRNA) via competing with IKKβ mRNA for binding miR-4741, consequently leading to upregulation and activation of IKKβ, and ultimately activation of NF-κB. The abnormally elevated IKBKBAS in LUAD was mainly resulted from the extremely decrease of miR-512-5p that targeting IKBKBAS. Furthermore, we identified a positive feedback loop between NF-κB and IKBKBAS, in which NF-κB activation induced by overexpression of IKBKBAS could promote the transcription of IKBKBAS by binding the κB sites within IKBKBAS promoter. Our studies revealed that IKBKBAS was involved in the activation of NF-κB signaling by upregulating the expression of IKKβ, which made it serve as a potential novel target for therapies to LUAD.

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