IncRNA AC004943.2 regulates miR‐135a‐5p and PTK2/P13K axis to promote laryngeal squamous cell carcinoma progression
Ontology highlight
ABSTRACT:
SUBMITTER: Zhu X
PROVIDER: S-EPMC10964940 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Circular RNA (circRNAs) functions vital in the pathogenesis and progression of hepatocellular carcinoma (HCC). However, the expressions and functions of certain circRNAs on metastasis and proliferation of that cancer is still unclear. Bioinformation analysis and qRT-PCR indicated that CircC16orf62 was prominent upregulated in HCC of which the expression level was positively associated to cancer's malignant progression. Gain or loss-of-function studies indicated that the reduction of CircC16orf62 expression promotes the proliferation, invasion, and glycolysis of HCC in vitro and in vivo. The bioinformatic analysis found that miR-138-5p and PTK2 were the downstream target of CircC16or62. Then, the FISH(Fluorescence immunoin situ hybridization) and cell nucleoplasmic separation determined that CircC16orf62 located in the cell cytoplasm. Plasmid vectors or siRNAs were used to change the expression of CircC16orf62, miR-138-5p, and PTK2 in PC cell lines. CircC16orf62 functioned as a molecular sponge for miR-138-5p, and a competitive endogenous RNA for PTK2, promoting AKT/mTOR pathway activation. Our observations lead us to conclude that CircC16orf62 functions as an oncogene in HCC progression, behaving as a competitive endogenous RNA for miR-138-5p binding, thus activating the AKT/mTOR pathway. In conclusion, CircC16orf62 is an oncogene through the miR-138-5p/PTK2/Akt axis in HCC cells, indicating CircC16orf62 can be a therapeutic target with potentiality for liver cancer and a predictive marker for people with HCC.
| S-EPMC8190090 | biostudies-literature
Project description:Laryngeal squamous cell carcinoma (LSCC) is one of the most aggressive cancers that affect the head and neck region. Recent researches have confirmed that long non-coding RNAs (lncRNAs) present an emerging role in diversiform diseases including cancers. Prostate cancer-associated ncRNA transcript 6 (PCAT6) is an oncogene in lung cancer, cervical cancer, colon cancer and gastric cancer, but its role in LSCC is still unknown. In the current study, we attempted to figure out the role of PCAT6 in LSCC. RT-qPCR was to analyze PCAT6 expression in LSCC cells. Functional assays were to uncover the role of PCAT6 in LSCC. Mechanism assays were to explore the regulatory mechanism behind PCAT6 in LSCC. PCAT6 exhibited higher expression in LSCC cells and PCAT6 strengthened cell proliferation and inhibited cell apoptosis. Furthermore, lncRNA PCAT6 modulated notch receptor 3 expression and activated NOTCH signaling pathway via serving as a sponge for miR-4731-5p. Taken together, lncRNA PCAT6 was identified as an oncogene in LSCC, which revealed that PCAT6 might be used as potential therapeutic target for LSCC.
| S-EPMC11262867 | biostudies-literature
Project description:ObjectiveLong non-coding RNAs (lncRNAs) are closely associated with the pathogenesis of laryngeal squamous cell carcinoma (LSCC). This study aimed to investigate the roles of AC068768.1 in LSCC.MethodsExosomes were extracted by ultracentrifugation and identified by transmission electron microscopy (TEM) assay. The expression levels of mRNA and miRNA were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cellular functions were assesses through immunofluorescence, flow cytometry, colony formation, wound healing and transwell assays. Chromatin immunoprecipitation (ChIP) and luciferase assays were conducted to verify the binding of AC068768.1 by signal transducer and activator of transcription 3 (STAT3). Xenograft assays were performed to confirm the roles of AC068768.1 in LSCC, and hematoxylin-eosin (HE) staining was applied for histological analysis.ResultsLSCC cell-derived exosomes induced M2-like tumor-associated macrophages (TAM2) polarization, which promoted the proliferation, migration, and invasion of LSCCs. Knockdown of exosomal AC068768.1 inhibited M2 polarization and suppressed LSCC aggressiveness both in vitro and in vivo. Moreover, AC068768.1 sponged miR-139-5p, inducing the upregulation of neurogenic locus notch homolog protein 1 (NOTCH1). LSCCs adapted to TAM2 polarization in the tumor microenvironment via AC068768.1-mediated activation of the NOTCH1 pathway. Additionally, NOTCH1 activated STAT3.ConclusionThe AC068768.1/miR-139-5p/NOTCH1/STAT3 axis promotes the metastasis of LSCC. This finding may provide a novel target for LSCC therapy.
| S-EPMC11386030 | biostudies-literature
Project description:Accumulating evidence suggests that circular RNAs (circRNAs) may be a key contributor to oncogenesis. Yet, the function of circRNAs in laryngeal squamous cell carcinoma (LSCC) is still not clear. In this study, we examined the function of circRNA_103862 in LSCC progression by analyzing the tissue specimens collected from a patient with LSCC by using different LSCC cell models in vitro and an LSCC xenograft model in nude mice. We found that circRNA_103862 was frequently upregulated in the tissues of LSCC and was correlated with metastasis and prognosis of LSCC patients. Furthermore, circRNA_103862 downregulation could reduce proliferation, migration, and invasion ability of LSCC cells. In terms of mechanism exploration, miR-493-5p was sponged by circRNA_103862. Rescue experiments also showed that circRNA_103862 could achieve a carcinogenic effect by regulating miR-493-5p. Moreover, a luciferase reporter analysis showed that Golgi membrane protein 1 (GOLM1) is a downstream effector of miR-493-5p. In conclusion, our data suggested that circRNA_103862 promotes the proliferation of LSCC through targeting the miR-493-5p/GOLM1 axis, and it might serve as a potential prognosis marker and therapy target for LSCC.
| S-EPMC7405723 | biostudies-literature
Project description:Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are involved in the progression of laryngeal squamous cell carcinoma (LSCC). Here, we aimed to disclose the role of MNX1-AS1 in LSCC progression, and explore whether MNX1-AS1 participates in LSCC progression via targeting miR-744-5p to active BCL9/β-catenin signaling. Sixty-five human LSCC tissues and the paracancerous normal tissues were recruited to determine the levels of MNX1-AS1, miR-744-5p and BCL9 using qRT-PCR. The interaction of miR-744-5p and MNX1-AS1/BCL9 was determined by using the RNA immunoprecipitation (RIP) assay and/or luciferase gene reporter assay. Cell viability, in vivo tumor formation, invasion and migration abilities were detected by MTT, Xenograft models and Transwell assays. MNX1-AS1 level was increased significantly in human LSCC tissues as compared with the normal tissues, which showed a positive correlation with BCL9 level while a negative correlation with miR-744-5p level. High level of MNX1-AS1 predicted a poor prognosis and an advanced clinical process in LSCC patients. miR-744-5p targeted upregulation weakened the luciferase activity of MNX1-AS1 and /BCL9, and downregulated their expression levels-wt, while showed no effect when the binding sites were mutated. Knockdown of MNX1-AS1 markedly weakened cell viability, migration, and invasion abilities, while BCL9 overexpression abolished these tendencies. In addition, MNX1-AS1 downregulation induced decreases in tumor volumes and weights in vivo, accompanied by reductions in BCL9, Ki-67 and β-catenin expression and an increase in miR-744-5p expression. Collectively, this study reveals that MNX1-AS1 contributes to cell growth and migration by regulating miR-744-5p/BCL9/β-catenin axis in LSCC.
| S-EPMC8033468 | biostudies-literature
Project description:Previous studies find that long noncoding RNA human leukocyte antigen complex P5 (HCP5) is regarded as an oncogene via accelerating cancer cell growth, invasion, metastasis, vascularization, and drug resistance in renal cell carcinoma, gastric cancer, and colorectal cancer. Nevertheless, the effect and regulatory mechanism of HCP5 in laryngeal squamous cell carcinoma (LSCC) remains unknown. In this study, HCP5 expression levels were confirmed to be prominently raised in LSCC cell lines. HCP5 knockdown reduced cell proliferation and migration and invasive ability of LSCC cell lines. Furthermore, miR-216a-5p was confirmed to sponge HCP5, and its expression was prominently downregulated in LSCC cell lines and upregulated in HCP5-silenced LSCC cell lines. miR-216a-5p overexpression downregulated the cell proliferation and migration and invasive ability of LSCC cells. Additionally, the protein level of zinc finger E-box binding homeobox 1 (ZEB1), one target gene of miR-216a-5p, was highly expressed in LSCC cell lines, and its expression level was downregulated by HCP5 knockdown and miR-216a-5p overexpression. An miR-216a-5p inhibitor reversed the effect of HCP5 knockdown on the proliferation and migration and invasive ability of LSCC cells. In conclusion, knocking down HCP5 may be a strategy to suppress the malignant biological function via regulating miR-216a-5p/ZEB1. Therefore, HCP5 may become a prospective therapeutic target for LSCC.
| S-EPMC9561619 | biostudies-literature
Project description:Laryngeal carcinoma is the predominant kind of tumor seen under the category of head and neck malignancies. LncRNA MIR600HG affects tumor morphology in numerous cancer types. However, the function of MIR600HG in laryngeal cancer remains unclear. Protein and gene expressions were analyzed by using western blot and quantitative real time polymerase chain reaction. Cells proliferation and migration were evaluated by EdU and transwell assays. Flow cytometry was performed to detect cells apoptosis. The interaction between MIR600HG or B-cell translocation gene 2 (BTG2) and miR-424-5p was analyzed by dual luciferase reporter assay and RNA immunoprecipitation. The expression of MIR600HG in laryngeal cancer tissues was lower than that in normal tissues, and low expression of MIR600HG was associated with poor prognosis in laryngeal cancer. Furthermore, overexpression of MIR600HG resulted in a reduction in cellular proliferation and the promotion of apoptosis in both HEp-2 and Tu-212. Mechanically, miR-424-5p was a direct target of MIR600HG, and overexpression of MIR600HG reduced miR-424-5p expression. Furthermore, BTG2 was a target gene of miR-424-5p and miR-424-5p upregulation suppressed the expression of BTG2. In addition, overexpression of BTG2 inhibited laryngeal cancer progression, whereas MIR600HG knockdown or miR-424-5p overexpression reversed the role of BTG2. This work suggested that MIR600HG represses laryngeal tumor development by regulating the miR-424-5p/BTG2 axis, which provides new molecules for early diagnosis of laryngeal cancer in the future.
| S-EPMC11786319 | biostudies-literature
Project description:Physical exercise stimulates adult hippocampal neurogenesis and is considered a relevant strategy for preventing age-related cognitive decline in humans. The underlying mechanisms remains controversial. Here, we show that exercise increases proliferation of neural precursor cells (NPCs) of the mouse dentate gyrus (DG) via downregulation of microRNA 135a-5p (miR-135a). MiR-135a inhibition stimulates NPC proliferation leading to increased neurogenesis, but not astrogliogenesis, in DG of resting mice, and intriguingly it re-activates NPC proliferation in aged mice. We identify 17 proteins (11 putative targets) modulated by miR-135 in NPCs. Of note, inositol 1,4,5-trisphosphate (IP3) receptor 1 and inositol polyphosphate-4-phosphatase type I are among the modulated proteins, suggesting that IP3 signaling may act downstream miR-135. miR-135 is the first noncoding RNA essential modulator of the brain's response to physical exercise. Prospectively, the miR-135-IP3 axis might represent a novel target of therapeutic intervention to prevent pathological brain aging.
| S-EPMC6565832 | biostudies-literature
Project description:Laryngeal squamous cell carcinoma (LSCC) is a common form of head and neck cancer with poor prognosis. However, the mechanism underlying the pathogenesis of LSCC remains unclear. Here, we demonstrated increased expression of fascin actin-bundling protein 1 (FSCN1) and decreased expression of microRNA-145-5p (miR-145-5p) in a clinical cohort of LSCC. Luciferase assay revealed that miR-145-5p is a negative regulator of FSCN1. Importantly, low miR-145-5p expression was correlated with TNM (tumor, node, metastasis) status and metastasis. Moreover, cases with low miR-145-5p/high FSCN1 expression showed poor prognosis, and these characteristics together served as independent prognostic indicators of survival. Gain- and loss-of-function studies showed that miR-145-5p overexpression or FSCN1 knockdown inhibited LSCC migration, invasion, and growth by suppressing the epithelial-mesenchymal transition along with inducing cell-cycle arrest and apoptosis. Additionally, hypermethylation of the miR-145-5p promoter suggested that repression of miR-145-5p arises through epigenetic inactivation. LSCC tumor growth in vivo could be inhibited by using miR-145-5p agomir or FSCN1 small interfering RNA (siRNA), which highlights the potential for clinical translation. Collectively, our findings indicate that miR-145-5p plays critical roles in inhibiting the progression of LSCC by suppressing FSCN1. Both miR-145-5p and FSCN1 are important potential prognostic markers and therapeutic targets for LSCC.
| S-EPMC6369713 | biostudies-literature
Project description:Laryngeal squamous cell carcinoma (LSCC) is a common malignancy of the head and neck. Recently, circular RNA (circRNA) has been studied extensively in multisystem diseases. However, there are few research on biological functions and molecular mechanisms of circRNAs in LSCC. CircRNA array was used to detect the differentially expressed circRNAs. Kaplan-Meier and cox regression analysis were used to identify survival based on circMMP9. The qRT-PCR, RNase R treatment, sanger sequencing and in situ hybridization were used to verify circMMP9 expression, characteristics and localization in LSCC tissues and cells. Functionally, colony formation, MTS, transwell and in vivo assays were proceeded to detect the biological function of circMMP9 in LSCC progression. The RNA-seq was conducted to identify the molecular targets of circMMP9. Mechanically, MeRIP, RNA Immunoprecipitation (RIP), RNA pulldown, Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were carried on to verify the regulatory mechanism of circMMP9. CircMMP9 was discovered upregulated in LSCC tissues and cells, and high level of circMMP9 was associated with poor prognosis, low degree of pathological grading, high TNM stage and lymph node metastasis of LSCC. CircMMP9 knockdown prevented LSCC progression both in vitro and in vivo, whereas, circMMP9 overexpression had the opposite effect. CircMMP9 was stabilized by IGF2BP2 in m6A-dependent manner. TRIM59 was identified as downstream target of circMMP9. CircMMP9 recruited ETS1 to stimulate TRIM59 transcription. Moreover, TRIM59 accelerated LSCC progression via activating the PI3K/AKT signal pathway. Our findings offered a unique regulatory mechanism for circMMP9 in LSCC, as well as a novel proof that circMMP9 may be utilize as a diagnostic marker and therapeutic target for LSCC patients.
| S-EPMC10847447 | biostudies-literature