Modular scaffolding by lncRNA HOXA10-AS promotes oral cancer progression.
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ABSTRACT:
SUBMITTER: Chen YT
PROVIDER: S-EPMC9300705 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo study the role of long noncoding RNA HOXA10-AS in gastric cancer (GC) and its underlying mechanism which is one of the most common and fetal malignancies. Long noncoding RNA HOXA10-AS is highly expressed and acts in an oncogenic role in cancers. However, its roles in GC are still unknown.MethodsThe expression of HOXA10-AS and HOXA10 in GC tissues from the TCGA database was analyzed. Western blot and qRT-PCR assays were applied to examine the expression of HOXA10-AS and HOXA10. Cell proliferation was evaluated with CCK-8 and EdU incorporation assays. Cell apoptosis was analyzed by flow cytometry. Migratory and invasive capacities were evaluated with wound healing and transwell assays.ResultsHOXA10-AS and HOXA10 were upregulated in GC, and their expressions were positively correlated. Knockdown of HOXA10-AS inhibited HOXA10 expression in GC cells. Furthermore, knockdown of HOXA10-AS restrained GC cell proliferation, migration, and invasion but promoted apoptosis. In addition, overexpression of HOXA10-AS promoted malignant phenotypes of GC cells, but all these effects could be reversed by knockdown of HOXA10.ConclusionHOXA10-AS promoted GC cell proliferation, migration and invasion and enhanced apoptosis via upregulating HOXA10. Our study implies a novel regulatory mechanism of malignant phenotypes and provides potential therapeutic targets for GC.
| S-EPMC8866012 | biostudies-literature
Project description:Long noncoding RNAs (lncRNAs) have been demonstrated to play a role in carcinogenesis, but their mechanisms of function remain elusive. We explored the mechanisms of the oncogenic role of GCAWKR in gastric cancer (GC) using human tissues and cell lines. The in situ hybridization analysis was utilized to determine GCAWKR levels in samples from 42 GC patients and real-time qPCR in tissues from 123 patients. The GCAWKR levels were modulated in GC cell lines, and relevant biological and molecular analyses were performed. Levels of the GCAWKR were upregulated in GC tissues compared with normal tissues and associated with tumor size, lymph node metastasis, TNM stage, and patient outcomes. GCAWKR affected cell proliferation and cell invasion in multiple GC models. Mechanistically, GCAWKR bound WDR5 and KAT2A and acted as a molecular scaffold of WDR5/KAT2A complexes, modulating the affinity for WDR5/KAT2A complexes in the target gene's promoter region. Thus, our data defined a mechanism of lncRNA-mediated carcinogenesis in GC, suggesting new therapeutic targets in GC.
| S-EPMC6225079 | biostudies-literature
Project description:Due to the lack of effective early diagnostic measures and treatment methods, bladder cancer has become a malignant tumor that seriously threatens people's lives and health. Here, we reported that LINC00162, a super-enhancer long noncoding RNA, was highly expressed in bladder cancer cells and tissues. And LINC00162 was negatively correlated with neighboring PTTG1IP expression. Knocking down LINC00162 expression can inhibit the proliferative activity of bladder cancer cells and the growth of transplanted tumors in vivo, while knocking down the expression of PTTG1IP could restore the proliferative activity of bladder cancer cells. In addition, both LINC00162 and PTTG1IP were found to be able to bind to THRAP3, a transcription-related protein. And THRAP3 can regulate PTTG1IP expression. Finally, we demonstrated a mechanism that LINC00162 could regulate PTTG1IP expression through binding THRAP3. This study provided a potential target molecule for clinical treatment of bladder cancer.
| S-EPMC7736918 | biostudies-literature
Project description:BackgroundColorectal cancer is a digestive tract malignant tumor, ranking the second mortality and the third incidence cancer worldwide. The abnormal expression of NEAT1 is related to the occurrence and development of colorectal cancer. However, the specific mechanism of NEAT1 mediated-inflammatory pathway in the progression of colorectal cancer is still unclear.MethodsIn this study, expression of NEAT1 in colorectal cancer patients was analyzed by bioinformatics. Clinical samples including peripheral blood and colorectal cancer tissues were collected for qRT-PCR, Western blot, and immunohistochemistry assay. The role of NEAT1 in the colorectal cancer progression was further confirmed by both in-vivo and in-vitro functional experiments.ResultsBy bioinformatics prediction, it is found that NEAT1 expression level is significantly higher in the peripheral blood of patients with colorectal cancer and is associated with poor prognosis. In-vitro functional studies indicated that NEAT1 knockdown suppressed the proliferation and migration of colorectal cancer cells by mediating inflammatory response. In-vivo tumorigenesis experiments showed that NEAT1 knockdown suppressed tumor growth.ConclusionAbnormal high expression level of NEAT1 in colorectal cancer tissues and cells leads to poor prognosis. Mechanistically, NEAT1 triggers off the proliferation and migration of colorectal cancer cells through promoting the inflammatory reaction. Clinically, the expression level of NEAT1 in serum may be a marker for diagnosis and prognosis of colorectal cancer.
| S-EPMC9536976 | biostudies-literature
Project description:BackgroundGastric cancer (GC) is one of the most common cancers worldwide and the majority of GC patients are diagnosed at advanced stages due to the lack of early detection biomarkers. LncRNAs have been shown to play important roles in various diseases and could be predictive biomarkers and therapeutic targets. Our study demonstrated that low expression of lncRNA APTR could promote gastric cancer progression.MethodsDifferentiated expressed lncRNAs were identified through analyzing TCGA paired GC RNA sequencing data. LncRNA APTR's clinical relevance was analyzed using the TCGA dataset and GEO datasets. APTR expression in patient samples was detected through qPCR. The proliferation, colony formation, and migration of GC cells were tested. Bioinformatic analyses were performed to explore APTR-affected signaling pathways in GC.ResultsLncRNA APTR is lower expressed in gastric tumor samples and low expression of APTR predicts a poor diagnosis and outcome in GC patients. Silencing APTR promotes gastric cancer proliferation and invasiveness. APTR expression is negatively correlated with inflammatory signaling in the gastric tumor microenvironment.ConclusionOur study showed that low expression of lncRNA APTR in gastric cancer is correlated with tumorigenesis and poor diagnosis and prognosis, which is a potential biomarker for gastric cancer patients' diagnosis and treatment.
| S-EPMC9463576 | biostudies-literature
Project description:Transforming growth factor- (TGF-) signaling is a critical driver of epithelial–mesenchymal transition (EMT) and cancer progression. However, the regulatory roles of long non-coding RNAs (lncRNAs) in TGF--induced EMT and cancer progression are not well understood. Here, we identified an unannotated nuclear lncRNA LETS1 (LncRNA Enforcing TGF- Signaling 1) as a novel TGF-/SMAD target gene. Loss of LETS1 attenuates TGF--induced EMT, migration and extravasation in breast and lung cancer cells. LETS1 potentiates TGF-/SMAD signaling by stabilizing cell surface TGF- type I receptor (TRI) and thereby forms a positive feedback loop. Mechanistically, LETS1 inhibits TRI polyubiquitination by inducing the orphan nuclear receptor 4A1 (NR4A1) expression, a critical determinant of a destruction complex for inhibitory SMAD7. An unbiased interactome analysis identified the Nuclear Factor of Activated T Cells (NFAT5) as a protein partner of LETS1 to mediate activation of NR4A1 promoter. Overall, our findings characterize LETS1 as an EMT-promoting lncRNA and elucidate the mechanism by which nuclear LETS1 potentiates TGF- receptor signaling.
2023-07-31 | PXD037401 | Pride
Project description:Circular RNAs have been reported to play a vital role in the development and progression of various types of cancer. However, the underlying molecular role of circular RNA CTDP1 (circCTDP1) in the tumorigenesis of nasopharyngeal carcinoma (NPC) remains unknown. In the present study, circCTDP1 expression was found to be markedly upregulated in NPC tissues and cell lines (SUNE1, SUNE2 and 6?10B cell lines). Knockdown of circCTDP1 resulted in inhibition of proliferation, migration and invasion, and promoted apoptosis of NPC cells. Moreover, circCTDP1 directly interacted with microRNA (miR)?320b based on bioinformatics prediction and dual luciferase assay, and transfection with an miR?320b inhibitor reversed the effects of circCTDP1 knockdown on NPC cells. Furthermore, circCTDP1/miR?320b promoted NPC progression by regulating the expression of homeobox A10 (HOXA10). In addition, it was demonstrated that HOXA10 may exert its oncogenic role in NPC by regulating the expression of transforming growth factor ?2 (TGF?2). Taken together, these results revealed a novel regulatory mechanism, which may provide an improved understanding of NPC tumorigenesis and be useful in the development of potential targets for NPC therapy.
| S-EPMC7015121 | biostudies-literature
Project description:BCAR4 (Breast Cancer Anti-Estrogen Resistance 4) is a long noncoding RNA that was identified as an oncogene in breast cancer. In our research, we found that the expression level of BCAR4 was upregulated in colon cancer tissues compared to paired normal tissues. What's more, higher BCAR4 expression was correlated with lower survival rate in patients with colon cancer. Mechanistically, we showed that BCAR4 activated Wnt/?-catenin signaling in colon cancer by protecting ?-catenin from degradation. We also showed that BCAR4 overexpression promoted cell proliferation and migration in colon cancer. However, silencing BCAR4 inhibited cell growth and promoted apoptosis. Besides, BCAR4 knockdown decreased tumor growth in vivo. These findings indicate that BCAR4 facilitated colon cancer progression by enhancing cell proliferation and inhibiting apoptosis via BCAR4/?-catenin axis. BCAR4 may be a useful new target for treatment of patients with colon cancer.
| S-EPMC5696224 | biostudies-literature
Project description:BackgroundRecent reports suggest that the long non-coding RNA LBX2 antisense RNA 1 (LBX2-AS1) acts as an important regulator in cancer progression, but its significance in colorectal cancer (CRC) remains undetermined.MethodsLBX2-AS1 expression levels in CRC were determined from the GEPIA database and CRC tissues to investigate clinical relevance. meRIP-PCR assays investigated the molecular mechanisms underlying the function of m6A in LBX2-AS1. Loss of function experiments was used to define the role of LBX2-AS1 in the progression of CRC. The ceRNA function of LBX2-AS1 was evaluated by RNA immunoprecipitation. In vitro and PDX models were used to determine if LBX2-AS1 promotes 5-fluorouracil resistance.ResultsData from the TCGA and our institutional patient cohorts established that LBX2-AS1 levels were significantly upregulated in most CRC tissues relative to normal adjacent colon tissues. Moreover, LBX2-AS1 levels were positively correlated with aggressive disease characteristics, constituting an independent prognostic indicator of overall patient survival. Mechanistic investigations suggested that the increased LBX2-AS1 in CRC was mediated by METTL3-dependent m6A methylation. In vitro experiments indicated that knockdown of LBX2-AS1 inhibited CRC proliferation, migration and invasion with this phenotype linked to LBX2-AS1-mediated regulation of AKT1, acting as a ceRNA to sponge miR-422a. Ex vivo analysis of patient-derived CRC xenografts showed that low LBX2-AS1 expression cases exhibited 5-FU responsiveness and clinical investigations confirmed that low LBX2-AS1 expression was associated with improved clinical benefits from 5-FU therapy.ConclusionsTogether these results suggest that LBX2-AS1 may serve as a therapeutic target and predictor of 5-FU benefit in CRC patients.
| S-EPMC8449476 | biostudies-literature
Project description:The importance of long noncoding RNA (lncRNA) in tumorigenesis has been supported by increasing evidence in recent years. However, the mechanism linking lncRNA function with cancer progression remains poorly understood. lncRNA LCPAT1 plays a role in lung cancer. However, how it works in breast cancer (BC) is largely unclear. In this study, we found that LCPAT1 was highly expressed in BC tissues and cell lines. High LCPAT1 expression predicted a low survival rate in BC patients. LCPAT1 promoted BC cell proliferation, migration, and invasion while inhibiting apoptosis in vitro. LCPAT1 knockdown suppressed BC growth in vivo and vice versa. LCPAT1 interacted with RBBP4 and recruited it to the MFAP2 (microfibril-associated protein 2) promoter and then activated MFAP2 transcription. Restoration of MFAP2 rescued the effects of LCPAT1 knockdown in BC cells. In sum, LCPAT1 promotes BC progression through recruiting RBBP4 to initiate MFAP2 transcription.
| S-EPMC7424176 | biostudies-literature