LncRNA ODRUL Contributes to Osteosarcoma Progression through the miR-3182/MMP2 Axis.
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ABSTRACT:
SUBMITTER: Zhu KP
PROVIDER: S-EPMC5628795 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Long noncoding RNAs (lncRNAs) have been certified as important regulators in tumorigenesis. LncRNA GAS6-AS2 (GAS6-AS2) was a newly identified tumor-related lncRNA, and its dysregulation and oncogenic effects in melanoma and bladder cancer had been reported in previous studies. However, the expression pattern and potential function of GAS6-AS2 in osteosarcoma (OS) have not been investigated. In this study, we identified a novel OS-related lncRNA GAS6-AS2. We found that GAS6-AS2 was distinctly upregulated in both OS specimens and cell lines. Distinct up-regulation of GAS6-AS2 in OS was correlated with advanced clinical stages and shorter survivals. In addition, USF1 could directly bind to the GAS6-AS2 promoter and contribute to its overexpression. Furthermore, GAS6-AS2 knockdown caused tumor suppressive effects via reducing cellular proliferation, migration and invasion, and promoting OS cell apoptosis. Besides, GAS6-AS2 directly bound to miR-934 and downregulated its expression. Mechanistically, GAS6-AS2 positively regulated the expression of BCAT1 through sponging miR-934. Taken together, our data illustrated how GAS6-AS2 played an oncogenic role in OS and might offer a potential therapeutic target for treating OS.
| S-EPMC7185141 | biostudies-literature
Project description:The treatment of patients with advanced-stage osteosarcoma represents a major challenge, with very few treatments currently approved. Although accumulating evidence has demonstrated the importance of lncRNAs in osteosarcoma, the current knowledge on the functional roles and molecular mechanisms of lncRNA endogenous born avirus-like nucleoprotein (EBLN3P) is limited. At present, the expressions of EBLN3P and miR-224-5p in osteosarcoma tissues were quantified by reverse transcription-quantitative PCR assay, and the expression of Ras-related protein 10 (Rab10) in osteosarcoma tissues was quantified by immunohistochemistry and western-blotting. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P, Rab10 and miR-224-5p. The regulatory role of EBLN3P or miR-224-5p on cell proliferation, migration and invasion ability were verified by Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interaction among EBLN3P, miR-224-5p and Rab10 were testified by luciferase. The increased expression of EBLN3P and Rab10 and decreased expression of miR-224-5p were observed in osteosarcoma tissues and cell lines. Besides, the overexpression of EBLN3P or knockdown of miR-224-5p were revealed to promote the proliferation, migration and invasion of osteosarcoma cells. Bioinformatics analysis and luciferase assay revealed that EBLN3P could directly interacted with miR-224-5p to attenuate miR-224-5p binding to the Rab10 3'-untranslated region. Furthermore, the mechanistic investigations revealed activation of the miR-224-5p/Rab10 regulatory loop by knockdown of miR-372-3p or overexpression of Rab10, thereby confirming the in vitro role of EBLN3P in promoting osteosarcoma cell proliferation, migration and invasion. To the best of our knowledge, the present study is the first to demonstrate that EBLN3P may act as a competitive endogenous RNA to modulate Rab10 expression by competitive sponging to miR-224-5p, leading to the regulation of osteosarcoma progression, which indicates a possible new approach to osteosarcoma diagnosis and treatment.
| S-EPMC7820338 | biostudies-literature
Project description:Osteosarcoma (OS) originates in the skeletal system and has a rising global incidence. Long Non-coding RNAs (lncRNAs) are key regulators of human cancers development and progression. However, their roles in the development of OS are not well understood. This research aimed to investigate the effect of a long non-coding RNA (lncRNA), MRUL, on OS and revealed its potential molecular mechanisms. The bioinformatics analysis demonstrated that lncRNA MRUL was involved in regulating nucleic acid-templated transcription, cellular macromolecule biosynthetic process, immune response, and inflammatory response. In this work, the expression of lncRNA MRUL was detected by quantitative real-time polymerase chain reaction (qRT-RCR) in both cancer tissues and cell lines. We found that lncRNA MRUL was up-regulated in cancer tissues and cell lines. Functional experiments showed that knockdown of lncRNA MRUL inhibited OS cell proliferation, and metastasis. At the same time, we found that lncRNA MRUL interacted with miR-125a-5p to suppress FUT4 expression. Moreover, inhibition of miR-125a-5p abrogated the biological roles of lncRNA MRUL knockdown on OS cell proliferation, migration, and invasion. In conclusion, these results demonstrated that OS-upregulated lncRNA MRUL promoted cell proliferation, and metastasis via negatively regulating miR-125a-5p, and imply that lncRNA MRUL may be a potential biomarker for OS.
| S-EPMC7330113 | biostudies-literature
Project description:Background:Long non-coding RAN five prime to Xist (LncRNA FTX) has been revealed to be a cancer-related lncRNA and implicated in the progression of colorectal cancer (CRC). Besides, miR-192-5p (miR-192) or eukaryotic initiation factor 5A2 (EIF5A2) also was identified to link with the tumorigenesis of CRC. Here, we further explored the function of FTX and the regulatory relationship among FTX, miR-192 and EIF5A2 in CRC progression. Methods:Levels of FTX, miR-192-5p and EIF5A2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot, respectively. Cell proliferation, apoptosis, migration and invasion were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry or transwell assay, respectively. The interaction between miR-192-5p and FTX or EIF5A2 was confirmed by dual-luciferase reporter and pull-down assay. Murine xenograft model was established using LoVo cells transfected with sh-FTX. Results:FTX was up-regulated in CRC tissues and cell lines, knockdown of FTX inhibited CRC cell proliferation, migration and invasion in vitro as well as suppressed CRC tumor growth in vivo. FTX was confirmed to directly bind to miR-192-5p and negatively regulated miR-192-5p expression in CRC cells. Besides that overexpressed FTX positively modulated EIF5A2, a direct target of miR-192-5p, via miR-192-5p in CRC cells. Importantly, the inhibitory activities on CRC progression mediated by FTX deletion were reversed miR-192-5p down-regulation or EIF5A2 up-regulation. Conclusion:LncRNA FTX functioned as an oncogene to contribute to CRC progression by regulating miR-192-5p/EIF5A2 axis, providing a novel insight into the pathogenesis of CRC and a promising therapeutic target for CRC treatment.
| S-EPMC7127817 | biostudies-literature
Project description:ObjectivesWe examined the expression of Lnc-ZFAS1 in osteosarcoma and comprehensively evaluated its effects on osteosarcoma in vitro and vivo. Moreover, we revealed the regulatory mechanism between Lnc-ZFAS1 and miR-520b/miR-520e-mediated RHOC and provided a novel clue for ameliorating osteosarcoma.MethodThe expression of Long non-coding RNA Zinc Finger Antisense 1 (LncRNA ZFAS1) osteosarcoma tissues and normal tissues in the TCGA database was analyzed. Then, LncRNA ZFAS1 expression was further verified in clinical samples and osteosarcoma cell lines (U2OS and KHOS), as well as the human osteoblast cell line hFOB1.19 by qRT-PCR. Thereafter, LncRNA ZFAS1 was overexpressed or silenced to explore its effects on cell proliferation, apoptosis, migration, invasion, and Epithelial-Mesenchymal Transition (EMT). The fundamental mechanism through which Lnc-ZFAS1 affects osteosarcoma progression was further investigated and verified.ResultsWe found that LncRNA ZFAS1 was upregulated in osteosarcoma, and Lnc-ZFAS1 overexpression facilitated osteosarcoma cells proliferation, migration, invasion and EMT, while Lnc-ZFAS1 silence exerted reverse influence. Mechanistically, Lnc-ZFAS1 functionally acted as a sponger of microRNA-520b (miR-520b) and microRNA-520e (miR-520e) to up-regulate Ras Homologue C (RHOC). In addition, depleted Lnc-ZFAS1 restrained osteosarcoma cells proliferation, migration, and invasion, which could be rescued by RHOC overexpression. Lnc-ZFAS1 was upregulated in osteosarcoma and Lnc-ZFAS1 could exert promoted impact upon osteosarcoma cells proliferation, migration, invasion, and EMT in vitro.ConclusionsLnc-ZFAS1 acted sponger of miR-520b and miR-520e to promote RHOC, indicating that Lnc-ZFAS1/miR-520b/RHOC and Lnc-ZFAS1/miR-520e/RHOC axes might serve as potential therapeutic strategies against osteosarcoma.
| S-EPMC9727593 | biostudies-literature
Project description:BackgroundThe long non-coding (lnc) RNA activated by small nucleolar RNA host gene 16 (SNHG16), which has been reported to play a vital role in a number of different types of cancer, is a novel lncRNA. However, following an osteosarcoma (OS) study, the expression pattern, biological roles, clinical values and potential molecular mechanism of SNHG16 remain unclear. In the current study, we aimed to examine its expression and possible function in osteosarcoma (OS).MethodCell proliferation was measured by colony formation assay and Cell Counting Kit-8 (CCK-8) in vitro, and xenograft transplantation assay in vivo. Meanwhile, we used transwell chambers to test cell migration and invasion was evaluated. Cell cycle and apoptosis was evaluated by flow cytometry assay. Immunoblotting and qPCR analysis was carried out to detect protein and gene expression, respectively. Luciferase reporter assay was used to predict the potential downstream genes.ResultsThe present study demonstrated that SNHG16 is highly expressed in both the tissues of patients with OS, as well as OS cell lines, and its expression level was positively correlated with clinical stage and poor overall survival. Functional assays revealed that the depletion of SNHG16 inhibits OS growth, OS cell progression and promotes apoptosis both in vivo and in vitro. In addition, the present study revealed that microRNA-1285-3p expression levels can be decreased by SNHG16 acting as a 'sponge', and that this pathway takes part in OS tumor growth in vivo, and OS cell proliferation, invasion, migration and apoptosis in vitro.ConclusionsThe results from the present study demonstrate the role of lncRNA SNHG16 in OS progression, which is SNHG16 might exert oncogenic role in osteosarcoma (OS) by acting as a ceRNA of miR-1285-3p, and it may become a novel target in OS therapy.
| S-EPMC8022398 | biostudies-literature
Project description:BackgroundLong non-coding RNA (lncRNA) SNHG5 has been found to play an important role in tumors. Nevertheless, the function and mechanism of lncRNA SNHG5 in osteosarcoma (OS) remains unclear. The purpose of this study was to investigate whether lncRNA SNHG5 can regulate the occurrence and development of OS cells.MethodsWe performed quantitative real time PCR to detect the expression of lncRNA SNHG5 in OS cells. 143B, MG63 (knockdown) and U2OS, U2R (overexpression) cell lines were chosen for the function study of SNHG5. The effect of SNHG5, miR-212-3p, and SGK3 in OS cells was explored by MTT assays, clony formation, flow cytometry, transwell assays, wound healing assays, and cell spreading assays. Quantitative real-time PCR, Western blot analysis and luciferase assays were used to detect the interaction between lncRNA SNHG5 and miR-212-3p.ResultsIn this study, knockdown of lncRNA SNHG5 suppressed the growth and metastasis of OS cells, whereas the overexpression of SNHG5 produced an opposite result. Mechanistically, lncRNA SNHG5 functions as a sponger against miR-212-3p and suppresses the miR-212-3p/SGK3 signaling pathway. Introduction of miR-212-3p mimics or inhibitors reverses SNHG5 overexpression or silences the exerted tumor promoting or suppressing effect. In addition, our results showed that the function of SNHG5 can be rescued by miR-212-3p and can regulate the growth and metastasis of OS cells via SGK3, the downstream target of miR-212-3p.ConclusionsIn summary, our study demonstrated that lncRNA SNHG5 can regulate the proliferation and metastasis of OS cells through the miR-212-3p/SGK3 axis. This axis may provide a new target for future clinical treatment.
| S-EPMC6145323 | biostudies-literature
Project description:BackgroundOsteosarcoma (OS) is the most common primary malignant bone tumor in young people. Tumor-associated macrophages (TAMs) have been reported to play an important role in the development of osteosarcoma. However, the detailed molecular mechanisms remain largely unknown and need to be elucidated. Recently, exosomes have been reported as the crucial mediator between tumor cells and the tumor microenvironment. And a lot of lncRNAs have been reported to act as either oncogenes or tumor suppressors in osteosarcoma. In this research, we aim to explore the role of macrophages-derived exosomal lncRNA in osteosarcoma development and further elucidated the potential molecular mechanisms involved.MethodsTAMs were differentiated from human mononuclear cells THP-1, and a high-throughput microarray assay was used to analyze the dysregulated lncRNAs and miRNAs in osteosarcoma cells co-cultured with macrophages-derived exosomes. Western blot, qRT-PCR assays, and Dual-luciferase reporter assay were used to verify the interaction among LIFR-AS1, miR-29a, and NFIA. Cck-8, EdU, colony formation assay, wound-healing, and transwell assay were performed to explore the characterize the proliferation and metastasis ability of OS cells. And qPCR, Western blots, immunohistochemistry, and cell immunofluorescence were used to detect the expression of relative genes or proteins.ResultsIn this study, we found that THP-1-induced macrophage-derived exosomes could facilitate osteosarcoma cell progression both in vitro and in vivo. Then, the results of the high-throughput microarray assay showed that LIFR-AS1 was highly expressed and miR-29a was lowly expressed. Furthermore, LIFR-AS1 was identified as a miR-29a sponge, and NFIA was validated as a direct target of miR-29a. Functional assays demonstrated that knockdown of exosomal LIFR-AS1 could attenuate the promotion effects of macrophages-derived exosomes on osteosarcoma cell progression and miR-29a inhibition could reserve the effect of LIFR-AS1-knockdown exosomes. Correspondingly, NFIA-knockdown could partially reverse the tumor inhibition effect of miR-29a on osteosarcoma cells.ConclusionsTaken together, macrophages-derived exosomal lncRNA LIFR-AS1 can promote osteosarcoma cell proliferation, invasion, and restrain cell apoptosis via miR-29a/NFIA axis, which can act as a potential novel therapeutic target for osteosarcoma therapy.
| S-EPMC8017664 | biostudies-literature
Project description:Circular RNA‑lipoprotein receptor 6 (circ‑LRP6) serves a role in promoting the tumorigenesis of retinoblastoma, esophageal squamous cell cancer and oral squamous cell carcinoma; however, whether circ‑LRP6 demonstrates the same effect in osteosarcoma (OS) is yet to be fully elucidated. The present study aimed to analyze the expression, role and potential molecular mechanism of circ‑LRP6 in OS. The expression levels of circ‑LRP6, microRNA (miR)‑141‑3p, histone deacetylase 4 (HDAC4) and high mobility group protein 1 (HMGB1) were evaluated by reverse transcription-quantitative PCR in OS tissues and cell lines. Cell Counting Kit‑8, Transwell and Matrigel assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Western blotting was also performed to determine HDAC4 and HMGB1 protein expression levels. Bioinformatics and dual‑luciferase reporter assays were used to predict and analyze the interactions between circ‑LRP6 and miR‑141‑3p, miR‑141‑3p and HDAC4, as well as between miR‑141‑3p and HMGB1. Additionally, RNA immunoprecipitation was performed to verify the association between circ‑LRP6 and miR‑141‑3p. The results confirmed that circ‑LRP6 was highly expressed in OS tissues and cell lines. In addition, circ‑LRP6 negatively regulated the expression of miR‑141‑3p and, in turn, miR‑141‑3p negatively regulated HDAC4 and HMGB1 expression. Functional assays revealed that circ‑LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells, whereas the inhibition of miR‑141‑3p or the overexpression of either HDAC4 or HMGB1 partly reversed the inhibitory effect of circ‑LRP6 knockdown. In summary, the present study determined that circ‑LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells by regulating the miR‑141‑3p/HDAC4/HMGB1 axis.
| S-EPMC8878724 | biostudies-literature
Project description:BACKGROUND:Osteosarcoma is a malignancy that normally affects children, adolescents, and young adults. Although accumulating evidence has demonstrated the importance of HULC in osteosarcoma, little is reported about its functional roles and molecular mechanisms. METHODS:The expression of HULC and miR-372-3p in osteosarcoma tissues was quantified by qRT-PCR. The regulatory roles of HULC and miR-372-3p on cell proliferation, apoptosis, migration and invasion were determined by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays, respectively. The bioinformatics prediction software RAID v2.0 was used to predict the putative binding sites. The interactions among HULC, miR-372-3p and HMGB1 were explored by luciferase assay and western blot assay. RESULTS:Our results revealed elevated HULC and decreased miR-372-3p expression in both osteosarcoma tissues and cell lines. Overexpression of HULC or knockdown of miR-372-3p promoted osteosarcoma cell proliferation, migration and invasion and induced cell apoptosis. Bioinformatics and luciferase assays verified that HULC directly interacted with miR-372-3p to attenuate miR-372-3p binding to the HMGB1 3'-UTR. Furthermore, mechanistic investigations confirmed that activation of the miR-372-3p/HMGB1 regulatory loop by knockdown of miR-372-3p or overexpression of HMGB1 reversed the in vitro roles of HULC in promoting osteosarcoma cell proliferation, migration and invasion. CONCLUSION:Our study is the first to demonstrate that HULC may act as a ceRNA to modulate HMGB1 expression by competitively sponging miR-372-3p, leading to the regulation of osteosarcoma progression, which provides new insight into osteosarcoma diagnosis and treatment.
| S-EPMC7081592 | biostudies-literature