Cytoskeleton Regulator RNA Research Articles

Matrix stiffness-dependent regulation of immunomodulatory genes in human MSCs is associated with the lncRNA CYTOR

Cell-matrix interactions in 3D environments significantly differ from those in 2D cultures. As such, mechanisms of mechanotransduction in 2D cultures are not necessarily applicable to cell-encapsulating hydrogels that resemble features of tissue architecture. Accordingly, the characterization of molecular pathways in 3D matrices is expected to uncover insights into how cells respond to their mechanical environment in physiological contexts, and potentially also inform hydrogel-based strategies in cell therapies. In this study, a bone marrow-mimetic hydrogel was employed to systematically investigate the stiffness-responsive transcriptome of mesenchymal stromal cells. High matrix rigidity impeded integrin-collagen adhesion, resulting in changes in cell morphology characterized by a contractile network of actin proximal to the cell membrane. This resulted in a suppression of extracellular matrix-regulatory genes involved in the remodeling of collagen fibrils, as well as the upregulation of secreted immunomodulatory factors. Moreover, an investigation of long noncoding RNAs revealed that the cytoskeleton regulator RNA (CYTOR) contributes to these 3D stiffness-driven changes in gene expression. Knockdown of CYTOR using antisense oligonucleotides enhanced the expression of numerous mechanoresponsive cytokines and chemokines to levels exceeding those achievable by modulating matrix stiffness alone. Taken together, our findings further our understanding of mechanisms of mechanotransduction that are distinct from canonical mechanotransductive pathways observed in 2D cultures.

CYTOR-NFAT1 feedback loop regulates epithelial-mesenchymal transition of retinal pigment epithelial cells.

Epithelial mesenchymal transition (EMT) occurring in retinal pigment epithelial cells (RPE) is a crucial mechanism that contributes to the development of age-related macular degeneration (AMD), a pivotal factor leading topermanent vision impairment. Long non-coding RNAs (lncRNAs) have emerged as critical regulators orchestrating EMT in RPE cells. In this study, we explored the function of the lncRNA CYTOR (cytoskeleton regulator RNA) in EMT of RPE cells and its underlying mechanisms. Through weighted correlation network analysis, we identified CYTOR as an EMT-related lncRNA associated with AMD. Experimental validation revealed that CYTOR orchestrates TGF-β1-induced EMT, as well as proliferation and migration of ARPE-19 cells. Further investigation demonstrated the involvement of CYTOR in regulating the WNT5A/NFAT1 pathway and NFAT1 intranuclear translocation in the ARPE-19 cell EMT model. Mechanistically, CHIP, EMSA and dual luciferase reporter assays confirmed NFAT1's direct binding to CYTOR's promoter, promoting transcription. Reciprocally, CYTOR overexpression promoted NFAT1 expression, while NFAT1 overexpression increased CYTOR transcription. These findings highlight a mutual promotion between CYTOR and NFAT1, forming a positive feedback loop that triggers the EMT phenotype in ARPE-19 cells. These discoveries provide valuable insights into the molecular mechanisms of EMT and its association with AMD, offering potential avenues for targeted therapies in EMT-related conditions, including AMD.

Hepatocyte-derived exosomes deliver the lncRNA CYTOR to hepatic stellate cells and promote liver fibrosis.

Liver fibrosis is characterized by the activation and transformation of hepatic stellate cells (HSCs) induced by various injury factors. The degree of liver fibrosis can be significantly improved, but persistent injury factors present a significant therapeutic challenge. Hepatocytes are the most important parenchymal cell type in the liver. In this study, we explored the molecular mechanisms by which damaged liver cells activate HSCs through extracellular vesicles. We established a coculture model of LO2 and LX2 and validated its exosomal transmission activity. Subsequently, differentially expressed long noncoding RNAs (lncRNAs) were screened through RNA sequencing and their mechanisms of action as competing endogenous RNAs (ceRNAs) further confirmed using biological methods, such as FISH and luciferase assays. Damaged liver cells induced activation of LX2 and upregulation of liver fibrosis-related markers. Exosomes extracted and identified from the supernatant fraction contained differentially expressed lncRNA cytoskeleton regulator RNA (CYTOR) that competed with microRNA-125 (miR-125) for binding to glial cell line-derived neurotrophic factor (GDNF) in HSCs, in turn, promoting LX2 activation. MiR-125 could target and regulate both CYTOR and GDNF and vice versa, as verified using the luciferase assay. In an invivo model, damaged liver extracellular vesicles induced the formation of liver fibrosis. Notably, downregulation of CYTOR within extracellular vesicles effectively inhibited liver fibrosis. The lncRNA CYTOR in exosomes of damaged liver cells is upregulated and modulates the expression of downstream GDNF through activity as a ceRNA, providing an effective mechanism for activation of HSCs.

Integrated analysis of SKA1-related ceRNA network and SKA1 immunoassays in HCC: A study based on bioinformatic.

Hepatocellular carcinoma (HCC) poses a global health challenge. Effective biomarkers are required for early diagnosis to improve survival rates of patients with HCC. Spindle and kinetochore-associated complex subunits 1 (SKA1) is essential for proper chromosome segregation in the mitotic cell cycle. Previous studies have shown that overexpression of SKA1 is associated with a poor prognosis in various cancers. The expression, prognostic value, and clinical functions of SKA1 in HCC were evaluated with several bioinformatics web portals. Additionally, we identified target long non-coding RNAs (lncRNAs) and microRNAs by analyzing messenger RNA (mRNA)-miRNA and miRNA-lncRNA interaction data and elucidated the potential competing endogenous RNA (ceRNA) mechanism associated with SKA1. High SKA1 expression was associated with poor prognosis in patients with HCC. Furthermore, multivariate Cox regression analysis revealed that SKA1 expression was an independent prognostic factor for HCC. GO and KEGG analyses showed that SKA1 is related to the cell cycle checkpoints, DNA replication and repair, Rho GTPases signaling, mitotic prometaphase, and kinesins. Gene set enrichment analysis revealed that high levels of SKA1 are associated with cancer-promoting pathways. DNA methylation of SKA1 in HCC tissues was lower than that in normal tissues. Ultimately, the following 9 potential ceRNA-based pathways targeting SKA1 were identified: lncRNA: AC026401.3, Small Nucleolar RNA Host Gene 3 (SNHG3), and AC124798.1-miR-139-5p-SKA1; lncRNA: AC26356.1, Small Nucleolar RNA Host Gene 16 (SNHG16), and FGD5 Antisense RNA 1-miR-22-3p-SKA1; lncRNA: Cytoskeleton Regulator RNA (CYTOR), MIR4435-2 Host Gene, and differentiation antagonizing non-protein coding RNA-miR-125b-5p-SKA1. SKA1 expression levels significantly correlated with immune cell infiltration and immune checkpoint genes in the HCC tissues. SKA1 is a potential prognostic biomarker for HCC. This study provides a meaningful direction for research on SKA1-related mechanisms, which will be beneficial for future research on HCC-related molecular biological therapies and targeted immunotherapy.

Expression analysis of cytoskeleton regulator RNA and Cyclin Dependent Kinase Inhibitor 2B genes in breast cancer.

Breast cancer has been found to be associated with deregulation of several non-coding genes and mRNA coding genes. To assess expressions of CYTOR and CDKN2B in breast cancer and adjacent samples and find their relevance with clinical data. We enumerated expression level of CDKN2B and CYTOR in 43 newly diagnosed breast cancer samples and their adjacent specimens using real-time PCR method Expression data was judged using Wilcoxon matched-pairs signed rank test. CYTOR level was higher in tumors compared with adjacent tissues. Nevertheless, there was no difference in expression of CDKN2B between these two sets of tissues. ROC curve analysis showed that CYTOR levels can differentiate between tumoral and adjacent tissues with AUC, specificity and sensitivity values of 0.65, 37% and 92% (P= 0.017). There was a positive correlation between expression levels of CYTOR and CDKN2B genes in breast cancer tissues (r= 0.5 and P= 0.0008) as well as adjacent tissues (r= 0.79 and P< 0.0001). Relative expression level of CDKN2B in normal tissues was associated with clinical stage (P= 0.014). Moreover, relative expression level of CDKN2B in tumor tissues was associated with the body weight. There was no other association between expressions of CYTOR and CDKN2B and clinical or pathological variables. Cumulatively, this study offers evidence for involvement of these genes in the pathoetiology of breast cancer.

LncRNA CYTOR Facilitates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating SOX11 via Sponging miR-6512-3p.

Periodontal ligament stem cells (PDLSCs) are considered ideal cell sources for the regeneration of periodontal and alveolar bone tissue. Cytoskeleton Regulator RNA (CYTOR), a newly discovered long noncoding RNA, has been reported to function as competing endogenous RNA (ceRNA) and to be involved in many biological processes. However, its roles in PDLSC osteogenic differentiation remain unclear. Here, we firstly found CYTOR was mainly sublocalized in the cytoplasm of PDLSCs and CYTOR expression was increased during osteogenic differentiation of PDLSCs. By employing gain- and loss-of-function approaches, we then identified CYTOR overexpression promoted osteogenic differentiation of PDLSCs while CYTOR knockdown inhibited this process. Furthermore, bioinformatics analysis was utilized to show that both CYTOR and SOX11 mRNA contained the same seed sites for miR-6512-3p, which was further confirmed by dual luciferase reporter assay and RNA-binding protein immunoprecipitation. Notably, CYTOR conferred its functions by directly binding to miR-6512-3p and an inverse correlation between CYTOR and miR-6512-3p on the level on SOX11 and osteogenic differentiation of PDLSCs was obtained. Additionally, miR-6512-3p could bind to SOX11 mRNA 3' UTR and repressed SOX11 expression. Moreover, level of SOX11 was significantly increased during osteogenic differentiation of PDLSCs. Knockdown of SOX11 attenuated the increasing effect of CYTOR overexpression on osteogenic differentiation of PDLSCs. Collectively, these data supported that CYTOR positively modulated the expression of SOX11 through competitively binding to miR-6512-3p, thus promoting osteogenic differentiation of PDLSCs. The CYTOR/miR-6512-3p/SOX11 axis could be a novel therapeutic target for periodontal regeneration medicine.

Cytoskeleton regulator RNA expression on cancer-associated fibroblasts is associated with prognosis and immunotherapy response in bladder cancer

BackgroundDysregulation of long noncoding RNAs (lncRNAs) has been reported to be associated with multiple tumors where they act as tumor suppressors or accelerators. The lncRNA CYTOR was identified as an oncogene involved in many cancers, such as gastric cancer, colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. However, the role of CYTOR in bladder cancer (BCa) has rarely been reported. MethodsUsing cancer datasets from The Cancer Genome Atlas (TCGA) program, we analyzed the association between CYTOR expression and prognostic value, oncogenic pathways, antitumor immunity and immunotherapy response in BCa. The influence of CYTOR on the immune infiltration pattern in the urothelial carcinoma microenvironment was further verified in our dataset. Single-cell analysis revealed the role of CYTOR in the tumor microenvironment (TME) of BCa. Finally, we evaluated the expression of CYTOR in BCa in the Peking University First Hospital (PKU–BCa) dataset and its correlation with the malignant phenotype of BCa in vitro and in vivo. ResultsThe results indicated that CYTOR was highly expressed in multiple cancer samples, including BCa, and increased CYTOR expression contributed to poor overall survival (OS). Additionally, elevated CYTOR expression was significantly correlated with clinicopathological features of BCa, such as female sex, advanced TNM stage, high histological grade and non-papillary subtype. Functional characterization revealed that CYTOR may be involved in immune-related pathways and the epithelial mesenchymal transformation (EMT) process. Moreover, CYTOR had a significant association with infiltrating immune cells, including M2 macrophages and regulatory T cells (Tregs). CYTOR facilitates the crosstalk between cancer-associated fibroblasts (CAFs) and macrophages, and mediates M2 polarization of macrophages. Correlation analysis revealed a positive correlation between CYTOR expression and programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1)/expression and other targets for specific immunotherapy in BCa, which are recognized to predict the efficacy of immunotherapy. ConclusionsThese results suggest that CYTOR serves as a potential biomarker for predicting survival outcome, TME cell infiltration characteristics and immunotherapy response in BCa.

Long Noncoding RNA Cytoskeleton Regulator RNA Suppresses Apoptosis in Hepatoma Cells by Modulating the miR-125a-5p/HS1-Associated Protein X-1 Axis to Induce Caspase-9 Inactivation.

The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosis-related proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells. miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.

CYTOR Promotes Proliferation of Lung Cancer Cell by Targeting miR-103a-3p to Upregulate HMGB1.

Lung cancer is one of the most dangerous malignant tumors to human health in the world. Previous researches have shown that cytoskeleton regulator RNA (CYTOR), a long noncoding RNA was involved in the occurrence and development of various types of cancer. The aim of this study is to investigate the clinical significance and biological function of CYTOR in lung cancer. Real-time quantitative PCR was applied to detect the expression of CYTOR. The proliferation of A549 and H1299 cells was analyzed by CCK8 assay. The luciferase reporter assay and RNA pull-down assay were used to reveal the interactions between CYTOR and its downstream targets. Western blot was used to detect the expression of high-mobility group protein B1 (HMGB1). Here we found CYTOR was upregulated in lung cancer tissues and cell lines. The proliferation of A549 and H1299 cells was inhibited after CYTOR silencing. In addition, CYTOR could directly interact with and negatively regulate miR-103a-3p, and miR-103a-3p inhibited cell proliferation by targeting HMGB1. The CYTOR/miR-103a-3p/HMGB1 axis promoted lung cancer cell proliferation. CYTOR sponges miR-103a-3p to promote the proliferation of lung cancer cells through HMGB1. The CYTOR/miR-103a-3p/HMGB1 axis plays a critical role in the progression of lung cancer.

Long non-coding RNA CYTOR modulates cancer progression through miR-136-5p/MAT2B axis in renal cell carcinoma

BackgroundTo explore the role of long noncoding RNAs (lncRNAs) cytoskeleton regulator RNA (CYTOR) in renal cell carcinoma (RCC). MethodsThe levels of CYTOR in RCC tissues and cell lines were detected by RT-qPCR. 786-O and Caki-1 cells were transfected with CYTOR-shRNA or pcDNA-CYTOR respectively, or co-transfected with CYTOR-shRNA and miR-136-5p inhibitor, or co-transfected with miR-136-5p mimic and pcDNA-MAT2B. MTT assay, Transwell assay and flow cytometry were used to evaluate cell proliferation, invasion and apoptosis. The relationship between lncRNA CYTOR and miRNA-136-5p was detected by dual luciferase reporter gene and RNA pull down assays, and the targeted relationship between miRNA-136-5p and MAT2B was verified by dual luciferase reporter gene assay. The interaction between MAT2B and BAG3 protein was verified by co-IP experiment. The role of lncRNA CYTOR in vivo was also examined. ResultsLncRNA CYTOR was up-regulated in RCC tissues and cell lines, and miR-136-5p was down-regulated in renal carcinoma cell lines and tissues. Downregulation of CYTOR inhibited cell proliferation and invasion and promoted apoptosis. miR-136-5p was sponged by lncRNA CYTOR, which negatively regulated the development of RCC. MAT2B was a target gene of miR-136-5p. MAT2B protein interacted directly with BAG3 protein to affect the proliferation, invasion and apoptosis of RCC cells. In vivo experiments showed that the expression level of miR-136-5p was increased, and MAT2B expression was decreased after CYTOR knockdown, thereby inhibiting the development of RCC. ConclusionsLncRNA CYTOR promoted the progression of RCC by targeting miR-136-5p to regulate the target gene MAT2B, which interacted with BAG3 protein.

Long non-coding RNA (lncRNA) CYTOR promotes hepatocellular carcinoma proliferation by targeting the microRNA-125a-5p/LASP1 axis

ABSTRACT This study investigated the function of long non-coding RNA (lncRNA) cytoskeleton regulator RNA (CYTOR) in hepatocellular carcinoma (HCC). In HCC, the expression of CYTOR and microRNA (miR)-125a-5p were measured by quantitative real-time PCR (qRT-PCR). The expression of actin skeletal protein 1 (LASP1) was evaluated by Western blot analysis. Flow cytometry assays, transwell assays, colony formation assay, and cell counting kit-8 (CCK-8) assay were used to evaluate the roles of miR-125a-5p and CYTOR in HCC cells. The target genes of CYTOR and miR-125a-5p were identified by bioinformatics analysis and Luciferase assay. CYTOR was upregulated in HCC cell lines, and knockdown of CYTOR inhibited HCC cell growth. MiR-125a-5p was downregulated in HCC cells and a target of CYTOR in regulating HCC progression. Furthermore, LASP1 was a downstream target of miR-125a-5p. Finally, CYTOR was found to be involved in HCC progression in vivo. CYTOR promotes HCC development by regulating the miR-125a-5p/LASP1 axis.

LncRNA CYTOR promotes cell proliferation and tumor growth via miR-125b/SEMA4C axis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide with high morbidity and high mortality rates. Previous studies have demonstrated that cytoskeleton regulator RNA (CYTOR) plays critical roles in the tumorigenesis of various types of cancer. The present study aimed to investigate the clinical significance, biological function and molecular mechanism of CYTOR in the progression of HCC. The expression level of CYTOR was determined by reverse transcription quantitative PCR in HCC tissues and cell lines. The biological function of CYTOR was investigated using CCK-8 assay, EdU immunofluorescence, western blotting and TUNEL assay in vitro. A xenograft tumor model and immunohistochemistry were used to validate the role of CYTOR in vivo. The downstream targets of CYTOR and micro-RNA (miR)-125b were confirmed by RNA immunoprecipitation assay and luciferase reporter assays. The results demonstrated that CYTOR was significantly increased in HCC tissues compared with non-tumor tissues and that CYTOR expression was associated with the poor prognosis of patients with HCC. Furthermore, CYTOR silencing could inhibit the proliferation and promote the apoptosis of HCC cells. CYTOR overexpression had the opposite effects. The results from in vivo xenograft demonstrated that CYTOR knockdown suppressed tumor growth. In addition, CYTOR could directly interact with and negatively regulate miR-125b. Furthermore, semaphorin 4C (SEMA4C) was the target of miR-125b and CYTOR regulated SEMA4C expression by modulating miR-125b. Taken together, the findings from the present study demonstrated that CYTOR could promote cell proliferation and tumor growth by sponging miR-125b and upregulating SEMA4C, which suggested that CYTOR may act as a potential therapeutic target in HCC.

Forkhead box D1 promotes EMT and chemoresistance by upregulating lncRNA CYTOR in oral squamous cell carcinoma.

Chemotherapy regimens containing cisplatin remain the first-line treatments for patients with oral squamous cell cancer (OSCC); however, the treatment effect is often transient because of chemoresistance and recurrence. Understanding the mechanisms of chemoresistance in OSCC might provide novel targetable vulnerabilities. In the present study, we revealed that Forkhead box D1 (FOXD1) is upregulated in OSCC and predicted poor prognosis. Moreover, ectopic expression of FOXD1 promoted, while silencing of FOXD1 inhibited, the epithelial-mesenchymal transition (EMT) and chemoresistance of OSCC, both in vitro and in vivo. Mechanistically, FOXD1 binds to the promoter of long non-coding RNA Cytoskeleton Regulator RNA (CYTOR) and activates its transcription. CYTOR then acts as a competing endogenous RNA to inhibit miR-1252-5p and miR-3148, thus upregulating lipoma preferred partner (LPP) expression. Importantly, the CYTOR/LPP axis was proven to be essential for FOXD1-induced EMT and chemoresistance in OSCC. These findings reveal a novel mechanism for the chemotherapy resistance of OSCC, suggesting that FOXD1 might be a potential prognostic marker and anti-resistance therapeutic target.

LncRNA CYTOR attenuates sepsis-induced myocardial injury via regulating miR-24/XIAP.

This work aims to investigate the function and mechanism of long non-coding RNA (lncRNA) cytoskeleton regulator RNA (CYTOR) in myocardial injury induced by sepsis. The sepsis-induced myocardial injury model in mice was established by intraperitoneal injection of LPS (10 mg/kg) in vivo, and cardiomyocyte H9c2 was treated with LPS to mimic sepsis in vitro. CYTOR expression and miR-24 expression were detected by qRT-PCR. After up-regulation or down-regulation of CYTOR and miR-24 expression in the H9c2 cells, and the viability of the cells was detected via MTT assay, and cell apoptosis was detected by TUNEL assay. Western blot was applied to determine the expression level of caspase 3, Bax and X-chromosome-linked inhibitor of apoptosis (XIAP). Interaction between CYTOR and miR-24 was determined by bioinformatics analysis, RT-PCR and dual luciferase reporter assay. Interaction between miR-24 and XIAP was determined through bioinformatics analysis, RT-PCR, western blot and dual luciferase reporter assay. CYTOR was markedly down-regulated. CYTOR interacted with miR-24, and negatively regulated its expression level. Over-expression of CYTOR or transfection of miR-24 inhibitors significantly promoted viability and inhibited apoptosis of H9c2 cells, while the knockdown of CYTOR and transfection of miR-24 mimics had opposite effects. CYTOR suppressed the expression level of apoptosis-related proteins, but miR-24 increased them. miR-24 directly targeted the 3'UTR of XIAP, and suppressed it, and XIAP was modulated indirectly by CYTOR. Down-regulation of CYTOR aggravates sepsis-induced cardiac injury via regulating miR-24 and XIAP.

Role of LINC00152 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. The pathogenesis of NSCLC involves complex gene networks that include different types of non-coding RNAs, such as long non-coding RNAs (lncRNAs). The role of lncRNAs in NSCLC is gaining an increasing interest as their function is being explored in various human cancers. Recently, a new oncogenic lncRNA, LINC00152 (cytoskeleton regulator RNA (CYTOR)), has been identified in different tumor types. In NSCLC, the high expression of LINC00152 in tumor tissue and peripheral blood samples has been shown to be associated with worse prognoses of NSCLC patients. Overexpression of LINC00152 has been confirmed to promote the proliferation, invasion, and migration of NSCLC cells in vitro, as well as increase tumor growth in vivo. This review discusses the role of LINC00152 in NSCLC.

FOXM1/LINC00152 feedback loop regulates proliferation and apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via Wnt/β-catenin signaling pathway.

Rheumatoid arthritis (RA), a chronic systemic disease, is featured with inflammatory synovitis, which can lead to destruction on bone and cartilage and even cause disability. Emerging studies demonstrated that Fibroblast-like synoviocytes (FLS) is a vital cellular participant in RA progression. Long non-coding RNAs (lncRNAs) are also reported to participate in the pathogenesis of RA. In our present study, lncRNA microarray analysis was applied to screen out lncRNAs differentially expressed in RA FLS. Among which, cytoskeleton regulator RNA (LINC00152) presented biggest fold change. Gain- or loss-of function assays were further carried out in RA FLS, and the results revealed that LINC00152 promoted proliferation but induced apoptosis in RA FLS. Furthermore, up-regulation of LINC00152 may induce promotion of Wnt/β-catenin signaling pathway in RA FLS. Mechanistically, we found that forkhead box M1 (FOXM1) transcriptionally activated LINC00152 in RA FLS. Additionally, LINC00152 positively regulated FOXM1 via sponging miR-1270. In conclusion, the present study focused on elucidating the function of FOXM1/LINC00152 positive feedback loop in RA FLS and its association with Wnt/β-catenin signaling.

Long noncoding RNA cytoskeleton regulator RNA promotes cell invasion and metastasis by titrating miR-613 to regulate ANXA2 in nasopharyngeal carcinoma.

BackgroundNasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors. Long noncoding RNAs play critical roles in tumorigenesis.MethodsReal‐time quantitative PCR arrays were used to evaluate the expression levels of cytoskeleton regulator RNA (CYTOR) in NPC tissues and cells. Cell counting kit‐8 and colony formation analyses were used to test the NPC cell viability, while wound healing and transwell assays were employed to detect cell invasion and migration ability. Luciferase reporter assay and Western blot analyses were employed to explore the relationships among CYTOR, miR‐613, and ANXA2.ResultsWe found that CYTOR expression was elevated both in NPC tissues and cells. Functional assays revealed that CYTOR promoted the invasion and migration of NPC cells. The established spontaneous lymph node metastasis model also confirmed that CYTOR promoted NPC cell metastasis in vivo. Mechanically, we found that the subcellular localization of CYTOR mostly occurred in the cell cytoplasm. Luciferase reporter and RIP assays confirmed that CYTOR functioned as the molecular sponge of miR‐613. Subsequent experiments confirmed that ANXA2 was directly targeted by miR‐613. Gain‐ and loss‐of‐function studies further confirmed that CYTOR induced the upregulation of ANXA2 by competitively binding to miR‐613, thus leading to NPC metastasis.ConclusionOur results highlight the importance of CYTOR in NPC development and provide new insights into potential therapeutic targets for NPC.

LncRNA CYTOR promotes tamoxifen resistance inbreast cancer cells via sponging miR‑125a‑5p.

Development of resistance to endocrine therapy, such as tamoxifen, remains a tricky clinical problem during the treatment of breast cancer. Accumulating evidence suggested that dysregulation of long noncoding (lnc_RNAs contributes to the development of tamoxifen resistance. In the current study, via screening, cytoskeleton regulator RNA (CYTOR) was identified as the most significantly elevated lncRNA in the established tamoxifen resistant MCF7 cell lines (MCF7/TAM1 and MCF7/TAM2) compared with the parental MCF7 cells (MCF7-P). The CCK-8 assay indicated that silencing of CYTOR increased the sensitivity of MCF7/TAM1 and MCF7/TAM2 to tamoxifen treatment. Using bioinformatic analysis, it was predicted that microRNA (miR)-125a-5p might bind to CYTOR and the expression of miR-125a-5p was negatively correlated with CYTOR in the tumor tissues of breast cancer. In addition, RT-qPCR and dual luciferase assays validated that CYTOR directly repressed miR-125a-5p expression in breast cancer cells. Through regulation of miR-125a-5p, CYTOR elevated serum response factor (SRF) expression and activated Hippo and mitogen associated protein kinase signaling pathways to promote breast cancer cell survival upon tamoxifen treatment. In the collected tumor tissues of breast cancer in the present study, high expression of CYTOR was detected in tissues from patients with no response to tamoxifen compared with those from patients who were not treated with tamoxifen. A positive correlation between CYTOR and SRF mRNA expression was observed in tissues collected from patients with breast cancer. In conclusion, the results of the present study demonstrated a pivotal role of CYTOR in mediating tamoxifen resistance in breast cancer.

LncRNA-CYTOR Works as an Oncogene Through the CYTOR/miR-3679-5p/MACC1 Axis in Colorectal Cancer.

Pieces of evidence have shown that cytoskeleton regulator RNA (CYTOR), a long noncoding RNA (lncRNA), played a pivotal role in development and progression of a variety of cancers. In contrast, further research is needed to study the clinical significance and the detailed mechanism of action of lncRNA-CYTOR in colorectal cancer (CRC). This study aimed to investigate the clinical significance of CYTOR in CRC prognosis and identify the relevant potential signaling pathways and underlying mechanism of competing endogenous RNA. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) indicated that the expression of CYTOR was significantly elevated in CRC tumor tissues and cell lines. Aberrant expression of CYTOR was significantly related to TNM stage, T stage, N stage, and perineural and venous invasions. Survival analysis indicated that high-CYTOR expression was associated with poor overall survival in CRC patients (p = 0.0057), and multivariate analysis showed that high-CYTOR expression was an independent prognostic factor, which led to poor OS. In addition, bioinformatics analysis revealed that there were 18 microRNAs (miRNAs) interacted with CYTOR, and one of them, miR-3679-5p might collaborate with metastasis-associated in colon cancer-1 (MACC1), which was selected for further analysis. Pearson correlation analysis showed a significant positive correlation between the expression levels of CYTOR and MACC1. In conclusion, this study suggested that lncRNA-CYTOR played an important role in tumorigenesis and development through the CYTOR/miR-3679-5p/MACC1 axis.

Long non-coding RNA cytoskeleton regulator RNA (CYTOR) modulates pathological cardiac hypertrophy through miR-155-mediated IKKi signaling

Pathological cardiac hypertrophy, which may lead to heart failure and sudden death, can be affected by multiple factors. In our previous study, we revealed that IKKi deficiency induced cardiac hypertrophy through the activation of the AKT and NF-kB signaling pathway in response to aortic banding (AB). Non-coding RNAs, mainly long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a crucial role in normal developmental and pathological processes. In the present study, microarray analysis results from GEO database were analyzed, and upregulated lncRNAs in cardiac hypertrophy were identified. Of them, lncRNA cytoskeleton regulator RNA (CYTOR) obtained a fold-change of 6.16 and was positively correlated with IKBKE according to the data from The GTEx project. CYTOR knockdown significantly enhanced the inducible effect of AB operation on mice myocardial hypertrophy and Angiotensin II on cardiomyocyte hypertrophy. Moreover, miR-155 was significantly related to hypertrophic cardiomyopathy (HCM, |hsa05410) and predicted to target both CYTOR and IKBKE. Luciferase reporter and RIP assays revealed that CYTOR served as a ceRNA for miR-155 to counteract miR-155-mediated repression of IKBKE. Moreover, CYTOR knockdown reduced IKKi protein levels while activated NF-kB signaling pathway, whereas miR-155 inhibition exerted an opposing effect; the effect of CYTOR could be partially attenuated by miR-155 inhibition. Taken together, CYTOR might play a protective role in cardiac hypertrophy through miR-155 and downstream IKKi and NF-κB signaling, most possibly through serving as a ceRNA for miR-155 to counteract miR-155-mediated repression of IKBKE.