CircRPS16 Promotes Proliferation and Invasion of Hepatocellular Carcinoma by Sponging miR-876-5p to Upregulate SPINK1.
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ABSTRACT:
SUBMITTER: Lin S
PROVIDER: S-EPMC8476860 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe important role of long noncoding RNAs (lncRNAs) in cancer has been demonstrated in many studies. Prostate cancer gene expression marker 1 (PCGEM1) is a lncRNA specifically expressed within the prostate and overexpressed in many cancer cells. Numerous studies have shown that PCGEM1 promotes cell proliferation, invasion and migration. However, the specific mechanism of PCGEM1 within prostate cancer (PCa) has not been elucidated. MicroRNA-506-3p (miR-506-3p) is a noncoding RNA, and studies have indicated that miR-506-3p is downregulated in prostate cancer cell lines and functions as a tumor suppressor.MethodsThe TCGA (GEPIA) database ( http://gepia.cancer-pku.cn/ ) was employed to measure PCGEM1 levels in PCa. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the PCGEM1 gene level. CCK-8 (Cell Counting Kit-8) and colony formation assays were used to detect cell proliferation, and Transwell assays were applied to assess cell invasion and migration. The interacting ability of miR-506-3p with PCGEM1 or TRIAP1 was validated through a dual-luciferase reporter assay. TRIAP1 protein expression was detected by Western blotting.ResultsPCGEM1 expression was increased in PCa tissues and cells. In PCa tissues, High PCGEM1 expression was associated with high Gleason score, distant metastasis and extracapsular extension. In addition, PCGEM1 knockdown inhibited PCa cell (C4-2B and PC-3) proliferation, invasion and migration. miR-506-3p may interact with PCGEM1 or TRIAP1, and the suppressive effect of PCGEM1 knockdown was reversed when TRIAP1 or a miR-506-3p inhibitor was cotransfected.ConclusionPCGEM1 expression increased in PCa cells and tissues, enhancing PCa cell proliferation, migration and invasion by sponging miR-506 to upregulate TRIAP1.
| S-EPMC8808993 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) have displayed important roles in the development and progression of various cancers. However, the functions of the majority of circRNAs in osteosarcoma (OS) remain unknown.MethodsCircular RNA microarray analysis was performed in three OS cell lines (Saos-2, U2OS and MG63) and normal vascular endothelial cells. The co-differentially expressed circRNAs (CDECs) were identified in OS cell lines with the criterion of FDR (false discovery rate) < 0.05 and |fold change (FC)|> 2. Quantitative real-time PCR was used to validate the expression levels of selected CDECs. A series of functional assays, including MTT assay, flow cytometry and transwell assay were conducted in OS cells. The interaction between circRNA and miRNAs was confirmed by luciferase reporter assay and RNA immunoprecipitation assay.ResultsA total of 241 CDECs, including 75 upregulated and 166 downregulated CDECs, were identified in three OS cell lines compared with normal vascular endothelial cells. PCR validation showed that hsa_circ_0000704, hsa_circ_0001017 and hsa_circ_0005035 were all highly expression in the three OS cell lines, compared with osteoblast cell lines (HECC, hFOB1.19 and HFF-1). Functionally, overexpression of circ_0001017 significantly promoted the cell proliferation, migration and invasion and decreased apoptosis in U2OS cells. Knockdown of circ_0001017 obtained the opposite results. Circ_0001017 may downregulate miR-145-5p through direct binding. Furthermore, the expression of miR-145-5p was negatively regulated by circ_0001017 in OS cells. In addition, further functional studies indicated that miR-145-5p inhibitor eliminated the effects caused by si-circ_0001017 in OS cells.ConclusionsIn conclusion, our study suggested that circ_0001017 may be a novel oncogenic factor during the progression and development of OS by targeting miR-145-5p.
| S-EPMC8962139 | biostudies-literature
Project description:BackgroundLong noncoding RNAs (lncRNAs) have been identified as key players in promoting tumourigenesis in osteosarcoma. LncRNA OR3A4 (OR3A4) has been reported as an oncogene in a number of tumours. However, the clinical value of OR3A4 in osteosarcoma and the role of OR3A4 in osteosarcoma progression are still unknown.MethodsThe expression levels of OR3A4 in the tumour tissue of osteosarcoma patients and osteosarcoma cell lines were detected by RT-PCR. Kaplan-Meier analysis and log-rank test were performed to evaluate the relationship between the level of OR3A4 expression and the prognosis of osteosarcoma patients. We investigated the association between the tissue expression levels of OR3A4 and different clinicopathological characteristics of osteosarcoma patients by χ2 tests. Bioinformatic databases and luciferase reporter assays were used to predict and validate the target microRNA of OR3A4. Finally, the role of OR3A4 in the proliferation and invasion of osteosarcoma cells was tested by MTT and Transwell assays, respectively.ResultsWe observed that the expression level of OR3A4 was upregulated in the tumour tissue of osteosarcoma patients (p < 0.001) and osteosarcoma cell lines (p < 0.01) compared with the normal adjacent tissue and a normal human foetal osteoblastic cell line, respectively. The survival curve revealed that patients with high expression levels of OR3A4 had lower overall survival. Increased OR3A4 expression in osteosarcoma patients was associated with distant metastasis (p = 0.02) and advanced clinical stage (p < 0.001). In addition, bioinformatics analysis and luciferase reporter assays verified the complementary binding between OR3A4 and miR-1227-5p. Furthermore, we found that OR3A4 acted as a miR-1227-5p "sponge" to modulate osteosarcoma cell proliferation and invasion via downregulation of miR-1227-5p.ConclusionOR3A4 promotes osteosarcoma cell proliferation and invasion by sponging miR-1227-5p, which might be related to the metastasis of osteosarcoma and could be used as a potential prognostic biomarker and therapeutic target in osteosarcoma.
| S-EPMC7025082 | biostudies-literature
Project description:BackgroundAberrant expressions of long noncoding RNAs (lncRNAs) have been demonstrated to be related to the progress of HCC. The mechanisms that SNHG14 has participated in the development of HCC are obscure.MethodsQuantitative real-time PCR (qRT-PCR) was used to measure the lncRNA, microRNA and mRNA expression level. Cell migration, invasion and proliferation ability were evaluated by transwell and CCK8 assays. The ceRNA regulatory mechanism of SNHG14 was evaluated by RNA immunoprecipitation (RIP) and dual luciferase reporter assay. Tumorigenesis mouse model was used to explore the roles of miR-876-5p in vivo. The protein levels of SSR2 were measured by western blot assay.ResultsIn this study, we demonstrated that SNHG14 was highly expressed in HCC tissues, meanwhile, the elevated expression of SNHG14 predicted poor prognosis in patients with HCC. SNHG14 promoted proliferation and metastasis of HCC cells. We further revealed that SNHG14 functioned as a competing endogenous RNA (ceRNA) for miR-876-5p and that SSR2 was a downstream target of miR-876-5p in HCC. Transwell, CCK8 and animal experiments exhibited miR-876-5p inhibited HCC progression in vitro and in vivo. By conducting rescue experiments, we found the overexpression of SSR2 or knocking down the level of miR-876-5p could reverse the suppressive roles of SNHG14 depletion in HCC.ConclusionSNHG14 promotes HCC progress by acting as a sponge of miR-876-5p to regulate the expression of SSR2 in HCC.
| S-EPMC7824933 | biostudies-literature
Project description:TDO2 is a key enzyme in the kynurenine metabolic pathway, which is the most important pathway of tryptophan metabolism. It has been shown that miRNAs are involved in cell metastasis through interaction with target mRNAs. In this study, we found 645 miRNAs that could be immunoprecipitated with TDO2 through the RNA-immunoprecipitation experiment. miR-126-5p was selected as the research target, which was also confirmed by dual-luciferase reporter assay. Through qRT-PCR analysis, it was verified that the overexpression of miR-126-5p promoted the expression of TDO2, PI3K/AKT and WNT1. Meanwhile, it was verified that overexpression of miR-126-5p can promote intracellular tryptophan metabolism by HPLC. We also verified the effects of miR-126-5p on cell proliferation, migration, and invasion by cck-8, cell colony formation and trans-well assay in both HCCLM3 cells and HepG2 cells. In vivo experiments were also conducted to verify that miR-126-5p promoted tumor formation and growth via immunohistochemical detection of cell infiltration and proliferation to generate markers Ki-67, BAX, and VEGF. In conclusion, our results suggest that miR-126-5p is a biomarker and a potential new treatment target in the progression of HCC via promoting the expression of TDO2.
| S-EPMC8779717 | biostudies-literature
Project description:Hepatocellular Carcinoma (HCC) currently remains one of the most lethal malignancies worldwide. Recently, long non-coding RNAs (lncRNAs) had been demonstrated to play a crucial role in the progression of multiple human cancers, including HCC. In this study, we found that lncRNA DUXAP8 was upregulated in tumor samples and served as an oncogene in HCC. Bioinformatics analysis showed that DUXAP8 was significantly associated with the regulation of centrosome organization, homologous recombination, meiotic cell cycle process, sister chromatid segregation, nuclear chromosome segregation, and RNA export from the nucleus. The knockdown of DUXAP8 significantly suppresses cell proliferation and the cell cycle but induces cell apoptosis in HCC. Mechanically, the present study showed that DUXAP8 serves as a sponge of MiR-490-5p to promote the expression of BUB1 in HCC. Although the underlying regulatory mechanisms of DUXAP8 in HCC require further investigation, this study, for the first time, showed that DUXAP8 can serve as a new therapeutic target for HCC.
| S-EPMC7396656 | biostudies-literature
Project description:Circular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.
| S-EPMC8024300 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is the leading cause of tumor-related death worldwide due to high morbidity and mortality, yet lacking effective biomarkers and therapies. Circular RNAs (circRNAs) are a group of non-coding RNAs that regulate gene expression through interacting with miRNAs, implicating in the tumorigenesis and progression. A novel circRNA, circTP63, was reported to be an oncogene in HCC. However, its role in HCC remains unclear.MethodsqRT-PCR was used to assess the mRNA levels of CircTP63 in 90 pairs of tumor and adjacent normal tissues from HCC patients, one human normal hepatic epithelial cell line and HCC cell lines. CCK-8, colony formation, transwell, and flow cytometry assays were performed to detect the cellular function of circTP63/miR-155-5p/ZBTB18 in HCC cells. HCC xenograft mice models were established to assess the in vivo effect of circTP63. Bioinformatic analysis, RNA pull-down and luciferase assays were used to determine the interaction among circTP63/miR-155-5p/ZBTB18.ResultscircTP63 was significantly upregulated in HCC tissues and cell lines. High circTP63 expression is closely associated with the tumor stages, lymph node metastasis, and poor prognosis of HCC patients. Functionally, knockdown of circTP63 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of HCC. Meanwhile, overexpression of circTP63 enhanced HCC progression. Mechanically, circTP63 was a sponge of miR-155-5p to facilitate the ZBTB18 expression, and the ZBTB18 expression in HCC tissues was negatively associated with the survival rate of HCC patients. Furthermore, rescued assays revealed that the reduced tumor-promoting effect on HCC cells induced by knockdown of circTP63 can be reversed by miR-155-5p inhibitor or ZBTB18 overexpression.ConclusionOur data highlight a critical circTP63-miR-155-5p-ZBTB18 regulatory network involved in the HCC progression, gaining mechanistic insights into the function of circRNAs in HCC progression, and providing effective biomarkers and therapeutic targets for HCC treatment.
| S-EPMC7938576 | biostudies-literature
Project description:Breast cancer is the most common malignant tumor and the main cause of cancer-associated mortality in females worldwide. Long non-coding RNAs (lncRNAs) have been reported to play vital roles in breast cancer development and progression; however, our understanding of most lncRNAs in breast cancer is still limited. In this study, we demonstrated that small nucleolar RNA host gene 5 (SNHG5) promotes breast cancer cell proliferation both in vitro and in vivo, and depletion of SNHG5 significantly led to cell-cycle arrest at G1 phase. Accumulating evidence has shown that many lncRNA transcripts could function as competing endogenous RNAs (ceRNAs) by competitively binding common microRNAs (miRNAs). We found that SNHG5 acts as a sponge for miR-154-5p, reducing its ability to repress proliferating cell nuclear antigen (PCNA). SNHG5 promoted breast cancer proliferation and cell-cycle progression by upregulation of PCNA expression. Clinically, we observed an increased SNHG5 expression in breast cancer, whereas miR-154-5p was decreased in breast cancer tissues compared with the adjacent normal breast tissues. Furthermore, the SNHG5 expression was significantly negatively correlated with miR-154-5p expression. Taken together, our data uncover the SNHG5-miR-154-5p-PCNA axis and provide a novel mechanism to explain breast cancer proliferation.
| S-EPMC6606894 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) is currently the leading cause of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) play key roles in tumor occurrence and development as crucial cancer regulators. The present study aimed to explore the molecular mechanism and regulatory network of Linc00511 in LUAD and to identify new potential therapeutic targets for LUAD.MethodsReal-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine the relative Linc00511 levels in LUAD tissues and cells. The proliferation, apoptosis, migration, and invasion abilities of LUAD cells were assessed by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, flow cytometry, and a Transwell assay. Changes in hsa_miR-126-5p, hsa_miR-218-5p, and COL1A1 expression were analyzed using western blotting and RT-qPCR. Targeted binding between miR-126-5p/miR-218-5p and Linc00511 or COL1A1 was verified with a luciferase reporter system and confirmed by an RNA pulldown assay. The participation of the PI3K/AKT signaling pathway was confirmed via western blotting. Xenograft animal experiments were performed to detect the impact of Linc00511 on LUAD tumor growth in vivo.ResultsIn the present work, we observed that Linc00511 was upregulated in LUAD tissues and cells. Loss/gain-of-function experiments indicated that knockdown of Linc00511 significantly inhibited LUAD cell proliferation, migration and invasion and promoted LUAD cell apoptosis, whereas overexpression of Linc00511 showed the opposite effects. In addition, we determined that Linc00511 promoted COL1A1-mediated cell proliferation and cell motility by sponging miR-126-5p and miR-218-5p. Moreover, Linc00511 activated the PI3K/AKT signaling pathway through upregulation of COL1A1. Finally, silencing of Linc00511 inhibited LUAD tumor growth in vivo.ConclusionsLinc00511 acts as a competing endogenous RNA to regulate COL1A1 by targeting miR-126-5p and miR-218-5p, thereby promoting the proliferation and invasion of LUAD cells.
| S-EPMC9287882 | biostudies-literature