Hsa_circ_0053063 inhibits breast cancer cell proliferation via hsa_circ_0053063/hsa-miR-330-3p/PDCD4 axis.
Ontology highlight
ABSTRACT:
SUBMITTER: Ji C
PROVIDER: S-EPMC8064214 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Bladder cancer is a severe cancer with high mortality because of invasion and metastasis. Growing evidence has revealed that circular RNAs play critical roles in biological function, which is closely connected to proliferation and invasion of bladder cancer. In our study, we employed qRT-PCR, RNA fluorescence in situ hybridization (FISH), 5-ethynyl-2'-deoxyuridine (EdU), CCK-8, Transwell assays, luciferase reporter assays, xenografts, and live imaging to detect the roles of circular RNA binding protein with multiple splicing (circRBPMS) in bladder cancer (BC). Bioinformatics analysis and WB were performed to investigate the regulatory mechanism. Expression profile analysis of circular RNAs (circRNAs) in BC revealed that circRBPMS was significantly downregulated. Low circRBPMS expression correlates with aggressive BC phenotypes, whereas upregulation of circRBPMS suppresses BC cell proliferation and metastasis by directly targeting the miR-330-3p/ retinoic acid induced 2 (RAI2) axis. miR-330-3p upregulation or silencing of RAI2 restored BC cell proliferation, invasion, and migration following overexpression of circRBPMS. RAI2 silencing reversed miR-330-3p-induced cell invasion and migration as well as growth inhibition in vitro. Moreover, through bioinformatic analysis of the downstream target of RAI2 in the TCGA database, we identified and validated the biological role of circRBPMS through the RAI2-mediated ERK and epithelial-mesenchymal transition (EMT) pathways. We summarize the circRBPMS/miR-330-3p/RAI2 axis, where circRBPMS acts as a tumor suppressor, and provide a potential biomarker and therapeutic target for BC.
| S-EPMC7868720 | biostudies-literature
Project description:Lymphatic metastasis is the most common form in breast cancer (BC) progression. Previously, we observed that lnc045874, a most conservative homology of Homo Sapiens NONHSAT021545 (lnc021545), miR-330-3p, and EREG may have some effects in mouse hepatocarcinoma cell lines with different lymphatic metastasis potentials. Through data from TCGA and GEO database analysis, we speculated that miR-330-3p might be a tumor promoter, while EREG could be a tumor suppressor in BC. MiR-330-3p was upregulated, while lnc021545 and EREG were downregulated in 50 BC tissues. MiR-330-3p advanced the metastatic behaviors of BC cells, whereas lnc021545 and EREG resulted in the opposite effects. The three molecules' expressions were correlated respectively and showed that miR-330-3p targeted lnc021545 and EREG to affect their expressions. Lnc021545/miR-330-3p axis affected BC metastasis by regulating EREG in epithelial-to-mesenchymal transition. In 50 BC patients, these three molecules and their cooperation are associated with aggressive tumor phenotypes, patient outcomes, and trastuzumab therapy. We finally discovered that lnc021545, miR-330-3p, and EREG formed a multi-gene co-regulation system that affected the metastasis of BC and the cooperation reflects the synergistic effects of the three molecules, recommending that their cooperation may provide a more accurate index for anti-metastasis therapeutic and prognostic evaluation of BC.
| S-EPMC10094950 | biostudies-literature
Project description:BackgroundHyaluronan (HA) metabolism by chondrocytes is important for cartilage development and homeostasis. However, information about the function of circular RNAs (circRNAs) in HA metabolism is limited. We therefore profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis (OA).MethodsCircHYBID function in HA metabolism in chondrocytes was investigated using gain-of-function experiments, and circHYBID mechanism was confirmed via bioinformatics analysis and luciferase assays. The expression of circHYBID-hsa-miR-29b-3p-transforming growth factor (TGF)-β1 axis was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. CircHYBID, TGF-β1, and HA levels in cartilage samples were evaluated using qRT-PCR and pathological examination. Enzyme-linked immunosorbent assay was used to assess HA accumulation in chondrocyte supernatant.ResultsCircHYBID expression was significantly downregulated in damaged cartilage samples compared with that in the corresponding intact cartilage samples. CircHYBID expression was positively correlated with alcian blue score. Interleukin-1β stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis showed that circHYBID upregulated TGF-β1 expression by sponging hsa-miR-29b-3p.ConclusionsOur results describe a novel HA-related circRNA that could promote HA synthesis and accumulation. The circHYBID-hsa-miR-29b-3p-TGF-β1 axis may play a powerful regulatory role in HA metabolism and OA progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.
| S-EPMC8165762 | biostudies-literature
Project description:The present study aimed to explore whether and how microRNA‑5580‑3p (miR‑5580‑3p) affected oral cancer (OC) cell phenotypes via regulation of laminin subunit γ2 (LAMC2). Bioinformatics analysis was used to identify miR‑5580‑3p/LAMC2, a novel interactome that, to the best of our knowledge, has not been studied previously in OC. In the present study, the expression levels of miR‑5580‑3p and LAMC2 were detected by reverse transcription‑quantitative PCR, while the protein expression levels of LAMC2 were identified using western blotting. To determine the effects of miR‑5580‑3p and LAMC2 in OC, a number of experiments, including Cell Counting Kit‑8, 5‑bromo‑2'‑deoxyuridine cell proliferation and wound healing migration assays, were performed using OC SCC‑4 and Cal‑27 cell lines. Additionally, luciferase reporter assays were employed to examine the interaction between miR‑5580‑3p and LAMC2 mRNA. The results demonstrated that miR‑5580‑3p expression was downregulated, while LAMC2 expression was upregulated in OC tissues and cell lines. In addition to the observation that miR‑5580‑3p promoted the malignant phenotypes of OC, it was also revealed that miR‑5580‑3p inhibited OC cell viability, proliferation and migration by suppressing LAMC2. Therefore, the present study suggested that miR‑5580‑3p and LAMC2 may be potential biomarkers and therapeutic targets for OC diagnosis and therapies in the future.
| S-EPMC8072311 | biostudies-literature
Project description:Background Based on existing evidence, microRNAs (miRs) are gene regulators that undertake key functions in the oncogenesis and tumor progression of every single human malignant disease, such as thyroid carcinoma (TC). Previous clinical findings showed that expression of miR-195 is down-regulated in TC, which implies that miR-195 may be practically involved in TC pathogenesis. Nevertheless, the function of hsa-miR-195-5p in TC is still largely unclear. Herein, we detected the conceivable involvement of hsa-miR-195-5p in TC cell proliferation. Methods Real time PCR examination was performed to assess the expression level of hsa-miR-195-5p in TC cell lines TPC-1 and B-CPAP. TPC-1 cells were transfected with either hsa-miR-195-5p mimics or hsa-miR-195-5p inhibitor. After confirmation of transfection efficiency, the effect of hsa-miR-195-5p on proliferation and cell cycle of TPC-1 cells was assessed. The expression of cyclin D1 and p21 was simultaneously detected by western blotting. Moreover, targetScan 6.2 was used to predict hsa-miR-195-5p target genes. Subsequently, luciferase reporter was performed to examine whether there is a possible binding of hsa-miR-195-5p to 3’-UTR of cyclin D1 mRNA. Furthermore, cyclin D1 mRNA and protein levels were measured to check whether hsa-miR-195-5p exerts its function at the post-transcriptional level. In addition, to explore the function of cyclin D1 in TPC-1 cells overexpressing hsa-miR-195-5p, cyclin D1 siRNA was used to silence the expression of cyclin D1 in TPC-1 cells overexpressing hsa-miR-195-5p. Results We quantified the expression of hsa-miR-195-5p in TC cells and normal thyroid cells and found a remarkable decrease in hsa-miR-195-5p expression in TC cells. Over-expression of hsa-miR-195-5p obviously resulted in downgraded proliferation of TC cells. Moreover, hsa-miR-195-5p caused cell arrest at the GO/G1 phase. Further in silico analyses and the dual-luciferase reporter assay confirmed that 3’-UTR of cyclin D1 is a direct target of hsa-miR-195-5p. Western blot analysis uncovered that hsa-miR-195-5p over-expression led to decreased levels of cyclin D1 and p21. In mechanistic analyses, we found that silencing of cyclin D1 reversed the inhibitory effect of hsa-miR-195-5p on the proliferation of TC cells, which indicates that hsa-miR-195-5p suppresses TC cell proliferation by adversely regulating cyclin D1. Conclusions We concluded that hsa-miR-195-5p is a candidate tumor-suppressor miRNA in TC and that the hsa-miR-195-5p/p21/cyclin D1 pathway could be a potential therapeutic target for TC.
| S-EPMC8799136 | biostudies-literature
Project description:Objective:The aim of this study was to investigate the role of XPD in migration and invasion of hepatocellular carcinoma (HCC) cells. Methods:The expression of XPD and miR-29a-3p was examined by western blot and qRT-PCR, cell proliferation was detected by MTT assay, cell migration was detected by transwell assay. TargetScan was used to predict potential targets of miR-29a-3p. Results:In this study, we found that the expression of XPD and miR-29a-3p was downregulated in HCC samples and HCC cell lines. XPD suppressed proliferation and migration of HCC cell via regulating miR-29a-3p expression. Target prediction analysis and dual-luciferase reporter assay confirmed Mdm2 and PDGF-B were direct targets of miR-29a-3p, and miR-29a-3p suppressed proliferation and migration of HCC cells via regulating the expression of Mdm2 or PDGF-B. Conclusions:Our data indicated that XPD suppressed cell proliferation and migration via miR-29a-3p-Mdm2/PDGF-B axis in HCC.
| S-EPMC6321695 | biostudies-other
Project description:Hypoxia impairs blood–brain barrier (BBB) structure and function, causing pathophysiological changes in the context of stroke and high-altitude brain edema. Brain microvascular endothelial cells (BMECs) are major structural and functional elements of the BBB, and their exact role in hypoxia remains unknown. Here, we first deciphered the molecular events that occur in BMECs under 24 h hypoxia by whole-transcriptome sequencing assay. We found that hypoxia inhibited BMEC cell cycle progression and proliferation and downregulated minichromosome maintenance complex component 2 (Mcm2) expression. Mcm2 overexpression attenuated the inhibition of cell cycle progression and proliferation caused by hypoxia. Then, we predicted the upstream miRNAs of MCM2 through TargetScan and miRanDa and selected miR-212-3p, whose expression was significantly increased under hypoxia. Moreover, the miR-212-3p inhibitor attenuated the inhibition of cell cycle progression and cell proliferation caused by hypoxia by regulating MCM2. Taken together, these results suggest that the miR-212-3p/MCM2 axis plays an important role in BMECs under hypoxia and provide a potential target for the treatment of BBB disorder-related cerebrovascular disease.
| S-EPMC9917047 | biostudies-literature
Project description:Based on the fact that very little was found in the literature on the question of potential molecules and mechanism for high risk of cancer in patients with psoriasis, this study was designed and performed based on bioinformatics analysis including WGCNA. The most striking result to emerge from the data is that BUB1B/hsa-miR-130a-3p axis, closely related to the development of psoriasis, also plays a remarkable role in multiple cancer development. The expression patterns of hsa-miR-130a-3p were found significantly changed in multiple tumors, which was also associated with prognosis. Additionally, hsa-miR-130a-3p was downregulated in lesion skin of psoriasis, but there was no difference in blood between psoriasis patients and normal controls. Circulating has-miR-130a-3p was found to have a higher level of blood in multiple tumor patients, suggesting that hsa-miR-130a-3p has the potential to be a blood biomarker for cancer risk assessment in patients with psoriasis.
| S-EPMC9522491 | biostudies-literature
Project description:BackgroundSauchinone is extracted from the root of Saururus chinensis and exhibits potent antitumor effects in various human cancers. However, how sauchinone is involved in breast cancer has not been well studied.MethodsCells apoptosis, cell proliferation, and cycle distribution were evaluated. Xenograft tumor mouse model was constructed to investigate the roles of sauchinone. The relevant protein expression was detected by western blot.ResultsWe found that sauchinone significantly reduced proliferation and survival, also induced apoptosis of MCF-7 and Bcap-37 cells in vitro. Sauchinone significantly increased miR-148a-3p expression, and human epidermal growth factor receptor (HER)-2 targeted on miR-148a-3p. Sauchinone exposure downregulated HER-2 expression whose overexpression partly eliminated the inhibitory effect of sauchinone. Further, sauchinone efficiently inhibited breast cancer progression through downregulating HER-2 expression in vivo.ConclusionOur results indicate that sauchinone efficiently inhibits breast cancer progression through regulating miR-148a-3p/HER-2 axis, suggesting that sauchinone could be an effective anticancer agent for breast cancer.
| S-EPMC10151132 | biostudies-literature
Project description:BackgroundMicroRNAs (miRs) are involved in the regulation of many processes that contribute to malignancy, including cell proliferation, radiation resistance, invasion and metastasis. The role of miR-330-3p, an miR upregulated in breast cancer, remains unclear.MethodsWe examine the association of miR-330-3p with distant relapse-free survival in the Oxford cohort of breast cancer patients. We also study miR-330-3p function using in vitro invasion and ex ovo metastasis assays. Using in vitro luciferase assays, we validate a novel target gene for miR-330-3p, Collagen And Calcium Binding EGF Domains 1 (CCBE1). We assess functional consequences of CCBE1 loss by using siRNA-mediated knockdown followed by in vitro invasion assays. Lastly, we examine the expression profile of CCBE1 in breast carcinomas in the Curtis and TCGA Breast Cancer data sets using Oncomine Platform as well as distant relapse-free and overall survival of patients in the Helsinki University breast cancer data set according to CCBE1 expression status.ResultsmiR-330-3p is enriched in breast cancer, and higher levels of miR-330-3p expression are associated with lower distant relapse-free survival in a cohort of breast cancer patients. Consistent with these observations, overexpression of miR-330-3p in breast cancer cell lines results in greater invasiveness in vitro, and miR-330-3p-overexpressing cells also metastasise more aggressively ex ovo. We identify CCBE1 as a direct target of miR-330-3p, and show that knockdown of CCBE1 results in a greater invasive capacity. Accordingly, in breast cancer patients CCBE1 is frequently downregulated, and its loss is associated with reduced distant relapse-free and overall survival.ConclusionsWe show for the first time that miR-330-3p targets CCBE1 to promote invasion and metastasis. miR-330-3p and CCBE1 may represent promising biomarkers in breast cancer.
| S-EPMC5482727 | biostudies-literature