LncRNA RPL29P2 promotes peritoneal fibrosis and impairs peritoneal transport function via miR-1184 in peritoneal dialysis.

Peritoneal dialysis (PD), hemodialysis and kidney transplantation are the three therapies to treat uremia. However, PD is discontinued for peritoneal membrane fibrosis (PMF) and loss of peritoneal transport function (PTF) due to damage from high concentrations of glucose in PD fluids (PDFs). The mechanism behind PMF is unclear, and there are no available biomarkers for the evaluation of PMF and PTF. Using microarray screening, we found that a new long noncoding RNA (lncRNA), RPL29P2, was upregulated in the PM (peritoneal membrane) of long-term PD patients, and its expression level was correlated with PMF severity and the PTF loss. In vitro and rat model assays suggested that lncRNA RPL29P2 targets miR-1184 and induces the expression of collagen type I alpha 1 chain (COL1A1). Silencing RPL29P2 in the PD rat model might suppress the HG-induced phenotypic transition of Human peritoneal mesothelial cells (HPMCs), alleviate HG-induced fibrosis and prevent the loss of PTF. Overall, our findings revealed that lncRNA RPL29P2, which targets miR-1184 and collagen, may represent a useful marker and therapeutic target of PMF in PD patients.

Long-term MNNG exposure promotes gastric carcinogenesis by activating METTL3/m6A/miR1184 axis-mediated epithelial-mesenchymal transition.

As the representative item of environmental chemical carcinogen, MNNG was closely associated with the onset of Gastric cancer (GC), while the underlying mechanisms remain largely unknown. Here, we comprehensively analyzed the potential clinical significance of METTL3 in multiple GC patient cohorts. Additionally, we demonstrated that long-term exposure to MNNG elevated METTL3 and EMT marker expression by in vitro and in vivo models. Furthermore, the depletion of METTL3 impacted the proliferation, migration, invasion, and tumorigenesis of MNNG malignant transformation cells and GC cells. By me-RIP sequencing, we identified a panel of vital miRNAs potentially regulated by METTL3 that aberrantly expressed in MNNG-induced GC cells. Mechanistically, we showed that METTL3 meditated miR-1184/TRPM2 axis by regulating the process of miRNA-118. Our results provide novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment.

m6A-modified circ_0124554 promotes colorectal cancer progression and radioresistance through the miR-1184/LASP1 pathway.

BACKGROUND: Circular RNAs (circRNAs) are believed to regulate the progression of various cancers including colorectal cancer (CRC). However, the role and mechanism of circ_0124554 in regulating the sensitivity of CRC to radiation remain unknown. METHODS: The RNA levels of circ_0124554, LIM and SH3 protein 1 (LASP1), and methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit (METTL3) were detected by quantitative real-time polymerase chain reaction. Protein expression was checked by western blot. Cell proliferation, apoptosis, migration, and invasion were investigated by 5-Ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry analysis, and transwell assay, respectively. The sensitivity of CRC cells to radiation was analyzed by cell colony formation assay. Xenograft mouse model assay was conducted to disclose the role of circ_0001023 in the sensitivity of tumors to radiation in vivo. The binding relationships among circ_0124554, miR-1184 and LASP1 were confirmed by a dual-luciferase reporter assay. m6A RNA immunoprecipitation assay was performed to identify the association of METTL3 with circ_0124554. RESULTS: Circ_0124554 expression was upregulated in CRC tissues and cells in comparison with normal colorectal tissues and cells. Circ_0124554 knockdown inhibited proliferation, migration and invasion and promoted apoptosis and radiosensitivity of CRC cells. Moreover, circ_0124554 depletion inhibited tumor formation and improved radiosensitivity in vivo. MiR-1184 was identified as a target miRNA of circ_0124554 and targeted LASP1. Additionally, LASP1 overexpression rescued circ_0124554 knockdown-mediated effects in CRC cells. METTL3 mediated m6A methylation of circ_0124554. Further, circ_0124554 overexpression attenuated METTL3 depletion-induced effects in CRC cells. CONCLUSION: m6A-modified circ_0124554 promoted CRC progression and radioresistance by inducing LASP1 expression through interaction with miR-1184.

Hsa_circ_0000073 promotes lipid synthesis of osteosarcoma through hsa-miR-1184/ FADS2 pathway.

PURPOSE: Osteosarcoma is one of the leading causes of cancer mortality in children and teenagers. Dysregulation of lipid metabolism has been reported to involve tumor progression. Our previous evidence has revealed that circular RNA hsa_circ_0000073 enhanced the proliferation and metastasis of osteosarcoma cells. However, the effect of hsa_circ_0000073 on the lipid metabolism of osteosarcoma remains unclear. In this paper, we focused on the effect of hsa_circ_0000073 in lipid metabolism and investigated a network among hsa_circ_0000073/ miR-1184 /FADS2 in osteosarcoma, which provides a new idea to treat osteosarcoma. METHODS: The osteosarcoma and its adjacent tissue samples were collected for further validation. qRT-PCR or western blot was employed to detect the expression of hsa_circ_0000073, miR-1184, and FADS2 in OS cells and tissues. Microarray analysis, mass spectrometry, metabolomics analysis, and bioinformatics analysis were used to explore the potential function and target gene of hsa_circ_0000073. Oil red o, Nile red staining, and Triglyceride content assay were adopted to confirm the effect of hsa_circ_0000073 on the lipid metabolism of OS. Dual-luciferase reporter assays and RNA immunoprecipitation were applied to construct and validate the ceRNA network of hsa_circ_0000073. The xenograft mouse model was taken to verify the effect of hsa_circ_0000073 on lipid metabolism in vivo. RESULTS: The results confirmed that hsa_circ_0000073 was raised in the tumor tissues more than its adjacent tissue. Moreover, the higher expression of hsa_circ_0000073 was associated with worse survival rates, advanced clinical stage, large tumor size, and metastasis. After hsa_circ_0000073 silence, the gene chip and metabolomics result implied that hsa_circ_0000073 expression is positively correlated with a 91 genes signature and 78 metabolites in MG-63 and Saos-2 cells. The bioinformatics analysis indicated that hsa_circ_0000073 might involve in the biological processes of lipid metabolism. Further loss and gain of function experiments affirmed that hsa_circ_0000073 could impact cell lipid synthesis. Mechanically, hsa_circ_0000073 favored the expression of FADS2 genes by sponging miR-1184. Consistent with these observations, silencing of hsa_circ_0000073 inhibited lipid synthesis in vivo xenograft mouse model. CONCLUSIONS: Our study revealed that hsa_circ_0000073 contributed to the lipid synthesis of osteosarcoma by decreasing the expression of miR-1184, thereby increasing FADS2, which provides new insights into treating osteosarcoma.

Downregulation of circular RNA hsa_circ_0087856 sensitizes bladder cancer cells to cisplatin through targeting miR-1184/CITED2 signaling.

CircRNAs are considered as one of the potential therapeutic targets of multiple cancers. According to accumulating evidence, circRNA regulates cancer progression by acting as a miRNA sponge. In the current work, our data discovered that hsa_circ_0087856 and CITED2 expression was increased, while miR-1184 expression was decreased in BC cell lines and tissues. Hsa_circ_0087856 expression negatively correlated with miR-1184, whereas positively correlated with CITED2. Hsa_circ_0087856 silencing suppressed BC tumor growth, and contributed to the inhibition of cisplatin to tumor growth. In cellular experiments, hsa_circ_0087856 increasing promoted BC cells proliferation, migration and invasion, and inhibited the cells apoptosis. Hsa_circ_0087856 increasing partly reversed the inhibition of cisplatin to BC cell proliferation and the promotion to cell apoptosis. Oppositely, hsa_circ_0087856 silencing could increase the sensitivity of BC cells to cisplatin. Hsa_circ_0087856 promoted CITED2 expression through binding with miR-1184 and inhibiting its expression. CITED2 increasing partly reversed the promotion of hsa_circ_0087856 silencing to cisplatin-induced BC cells apoptosis promotion and proliferation suppression. Overall, our results revealed the role of hsa_circ_0087856 that downregulation its expression could enhance the BC cells sensitivity to cisplatin by facilitating CITED expression via sponging miR-1184. Moreover, our research provided a potential therapeutic target for BC.

Hsa_circ_0008035 Knockdown Inhibits Bladder Cancer Progression through miR-1184/RAP2B Axis.

INTRODUCTION: Circular RNAs (circRNAs) are related to the pathogenesis and progression of bladder cancer (BC). This research aimed to investigate the role and mechanism of hsa_circ_0008035 (circ_0008035) in BC progression. METHODS: Circ_0008035, microRNA (miR)-1,184, and Ras-related protein 2B (RAP2B) levels were examined in BC via quantitative real-time polymerase chain reaction and Western blotting. Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine staining, flow cytometry, caspase-3 assay kit, transwell, and tube formation assays were conducted to estimate the effects of circ_0008035 on the malignant phenotypes of BC tumors. The interaction between RNAs and genes was evaluated via a dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft model of BC in nude mice was established to estimate the effect of circ_0008035 in BC in vivo. RESULTS: Circ_0008035 and RAP2B levels were upregulated, while miR-1184 abundance was downregulated in BC tissues and cells. Circ_0008035 knockdown constrained cell proliferation, migration, invasion and angiogenesis but promoted apoptosis in vitro. And circ_0008035 silencing curbed xenograft tumor growth in vivo. Circ_0008035 acted as a miRNA sponge for miR-1184. Circ_0008035 increased RAP2B expression by sponging miR-1184. MiR-1184 downregulation relieved the effects of circ_0008035 knockdown on BC progression. And RAP2B knockdown partly reversed the effects of miR-1184 overexpression on BC progression. CONCLUSION: Circ_0008035-mediated BC progression via regulating the miR-1184/RAP2B axis, providing a potential target for BC treatment.

CircHSPG2 knockdown attenuates hypoxia-induced apoptosis, inflammation, and oxidative stress in human AC16 cardiomyocytes by regulating the miR-1184/MAP3K2 axis.

Circular RNAs (circRNAs) have been identified as vital regulators in cardiovascular diseases, including acute myocardial infarction (AMI). In this study, the function and mechanism of circRNA heparan sulfate proteoglycan 2 (circHSPG2) in hypoxia-induced injury in AC16 cardiomyocytes were investigated. AC16 cells were stimulated with hypoxia to establish an AMI cell model in vitro. Real-time quantitative PCR and western blot assays were performed to quantify the expression levels of circHSPG2, microRNA-1184 (miR-1184), and mitogen-activated protein kinase kinase kinase 2 (MAP3K2). Counting Kit-8 (CCK-8) assay was used to measure cell viability. Flow cytometry was performed to detect cell cycle and apoptosis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the expression of inflammatory factors. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were used to analyze the relationship between miR-1184 and circHSPG2 or MAP3K2. In AMI serum, circHSPG2 and MAP3K2 mRNA were highly expressed and miR-1184 was down-regulated. Hypoxia treatment elevated HIF1α expression and repressed cell growth and glycolysis. Moreover, hypoxia promoted cell apoptosis, inflammation, and oxidative stress in AC16 cells. Hypoxia-induced circHSPG2 expression in AC16 cells. CircHSPG2 knockdown alleviated hypoxia-induced AC16 cell injury. CircHSPG2 directly targeted miR-1184, and miR-1184 targeted and suppressed MAP3K2. Inhibition of miR-1184 or overexpression of MAP3K2 abolished the alleviated effect of circHSPG2 knockdown on hypoxia-induced AC16 cell injury. Overexpression of miR-1184 relieved hypoxia-induced impairment in AC16 cells by MAP3K2. CircHSPG2 could regulate MAP3K2 expression through miR-1184. CircHSPG2 knockdown protected AC16 cells from hypoxia-induced injury by regulating the miR-1184/MAP3K2 cascade.

Hsa_circ_0010729 regulates H2O2-induced myocardial injury by regulating miR-1184/RIPK1 axis.

BACKGROUND: Ischemia-reperfusion (I/R) is an important risk factor for cardiovascular diseases (CVDs) and cardiac transplantation, as I/R can cause myocardial cell hypoxia/reoxygenation (H/R) injury. Recent research has shown that circular RNAs (circRNAs) may affect the progress of H/R-induced myocardial injury, but the mechanism remains unknown. Our work explored the role of circ_0010729 in H2O2-induced myocardial injury. METHODS: The levels of circ_0010729, microRNA-1184 (miR-1184) and mRNA of receptor interacting serine/threonine kinase 1 (RIPK1) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) in human cardiac myocytes (HCMs). Meanwhile, the protein level of RIPK1 was quantified by western blot analysis. Besides, the cell functions were examined by 5-Ethynyl-29-deoxyuridine (EdU) assay, flow cytometry assay, western blot and antioxidant indexes analysis. Furthermore, the interplay between miR-1184 and circ_0010729 or RIPK1 was detected by dual-luciferase reporter assay. Eventually, the in vivo experiments were applied to measure the role of circ_0010729. RESULTS: The levels of circ_0010729 RNA and RIPK1 protein were increased, and the miR-1184 was decreased in HCMs exposed to H2O2. In functional analysis, circ_0010729 deficiency restrained cell apoptosis and oxidative stress, whereas promoted cell proliferation in HCMs under H2O2 exposure. Moreover, miR-1184 inhibited the H2O2-induced myocardial injury by targeting RIPK1. Mechanistically, circ_0010729 acted as a miR-1184 sponge to regulate the level of RIPK1. CONCLUSION: Circ_0010729 promotes H2O2-induced myocardial injury, and thus circ_001729 may be targeted as a potential therapy for H/R-induced myocardial injury.

Circ_0000523 regulates miR-1184/COL1A1/PI3K/Akt pathway to promote nasopharyngeal carcinoma progression.

BACKGROUND: The present study is to investigate the biological functions and mechanisms of circular RNA_0000523 (circ_0000523) in nasopharyngeal carcinoma (NPC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to examine the expression levels of circ_0000523 and microRNA-1184 (miR-1184) in NPC tissues and cells. Collagen type 1 alpha 1 chain (COL1A1) expression was assessed by qRT-PCR and immunohistochemistry (IHC) assay. Cell proliferation, cell cycle progression, migration and invasion were examined by cell counting kit-8 (CCK-8), 5-bromo-2'-deoxyuridine (BrdU), flow cytometry and Transwell assays. Xenograft nude mouse models were used to investigate the metastatic potential of NPC cells in vivo. The binding relationships between circ_0000523 and miR-1184, and between miR-1184 and COL1A1 were detected by dual-luciferase reporter gene assay. The protein expressions of COL1A1, phosphatidylinositol 3-kinase (p85), phosphorylated (p)-p85, protein kinase B (Akt) and p-Akt were detected through Western blot. The DAVID database was used for the enrichment analysis of the potential targets of miR-1184. RESULTS: Circ_0000523 and COL1A1 mRNA expressions were significantly increased in NPC tissues and cell lines. Circ_0000523 overexpression promoted NPC cell proliferation and accelerated cell cycle progression, whereas miR-1184 overexpression reversed these effects; circ_0000523 knockdown suppressed NPC cell proliferation and induced cell cycle arrest, while miR-1184 inhibition counteracted these effects. MiR-1184 was the downstream target of circ_0000523, and COL1A1 was the target gene of miR-1184 and could be positively modulated by circ_0000523. COL1A1 overexpression increased the expression levels of p-p85 and p-Akt, whereas knocking down COL1A1 repressed their expressions. CONCLUSIONS: Circ_0000523 facilitates NPC progression through regulating the miR-1184/COL1A1 axis.

CircP4HB regulates ferroptosis via SLC7A11-mediated glutathione synthesis in lung adenocarcinoma.

Background: Circular ribonucleic acids (circRNAs) play a key role in the development of different types of cancer. Ferroptosis is a type of programmed cell death that contributes to cancer progression. However, the role of circRNAs in lung adenocarcinoma (LUAD) ferroptosis remains unclear. Methods: The gene expression levels of circRNA P4HB (circP4HB), microRNA-1184 (miR-1184) and Solute carrier family 7 member 11 (Slc7a11), also known as Xct were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Ferroptosis of established LUAD cells was induced by erastin. Cell viability was examined via Cell Counting Kit 8 assays. Ferroptosis was evaluated by malondialdehyde (MDA), Prostaglandin-endoperoxide Synthase 2 (Ptgs2), lipid reactive oxygen species (lipid ROS), and JC-1 detection. The mechanism of circP4HB/miR-1184/SLC7A11 was investigated by luciferase reporter assays, RNA immunoprecipitation, RNA pull-down, and western blot assays. A functional for circP4HB in vivo was determined using xenograft nude mice models. Results: CircP4HB expression levels were increased in LUAD. It triggered glutathione (GSH) synthesis and, therefore protected LUAD cells from ferroptosis induced by erastin. CircP4HB may function as a competing endogenous RNA by modulating miR-1184 to regulate SLC7A11. CircP4HB inhibited ferroptosis by regulating miR-1184/ SLC7A11-mediated GSH synthesis. In vivo, overexpression of circP4HB promoted tumor growth and inhibited ferroptosis. Conclusions: The circRNA, circP4HB acts as a novel ferroptosis suppressor in LUAD. Furthermore, circP4HB protects LUAD from ferroptosis via modulation of the miR-1184/SLC7A11 axis. Our findings identified circP4HB as a novel biomarker in LUAD and warrants further investigation in the early diagnosis and treatment of LUAD.

Hsa_circ_0001666 promotes non-small cell lung cancer migration and invasion through miR-1184/miR-548I/AGO1 axis.

Accumulating evidence has revealed that the dysregulation of circular RNAs (circRNAs) plays crucial roles in the occurrence and progression of cancers. However, the aberrant expression profile and dysfunction of circRNAs in non-small cell lung cancer (NSCLC) have not been fully explored. Herein, we discovered that a circRNA, hsa_circ_0001666 (circ0001666), was highly expressed in NSCLC tissues and cell lines, and it was positively correlated with NSCLC tumor pathological grade and lymph node metastasis. Moreover, Kaplan-Meier survival analysis implied that NSCLC patients with high circ0001666 expression were negatively correlated with favorable survival. Functionally, circ0001666 could promote migration and invasion of NSCLC cells in vitro and in vivo. Mechanistically, circ0001666 could act as a sponge to miR-1184/miR-548I and upregulate the expression of AGO1, thereby promoting the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway in NSCLC cells. Collectively, these findings demonstrated that circ0001666 could serve as an oncogene to promote the migration and invasion of NSCLC via a novel miR-1184/miR-548I/AGO1 axis, which might be a promising therapeutic target for NSCLC treatment.

Estrogen receptor ß2 (ERß2)-mediated upregulation of hsa_circ_0000732 promotes tumor progression via sponging microRNA-1184 in triple-negative breast cancer (TNBC).

BACKGROUND: The role of estrogen receptor ß (ERß) in the pathogenesis and development of breast cancer (BC) is controversial, and it is currently considered to play contradictory roles in different phenotypes. ERß2 is thought to promote the BC process, but its role in triple-negative breast cancer (TNBC) has not been reported. METHODS: In this study, we collected tumor tissues from 15 patients with TNBC and obtained a variety of TNBC cell lines as research objects. The plasmid vectors and RNA interference techniques were used to change the level of target genes in cells, quantitative PCR and Western Blots were used to detect gene expression levels, CCK-8 and EdU assay were used to detect cell growth, and Transwell was used to detect cell migration and invasion. Dual-luciferase gene reports and RNA immunoprecipitation (RIP) were used to verify gene targeting relationships. RESULTS: ERß2 was up-regulated in TNBC tissues and promoted the growth, migration, and invasion of TNBC cells. ERß2 regulated hsa_circ_0000732 expression by binding to SCARF1 promoter. Knockdown of hsa_circ_0000732 inhibited TNBC cell proliferation, migration, and invasion by upregulating miR-1184. CONCLUSION: Our present study found that ERß2 is upregulated in some TNBC cells and promotes TNBC cell growth, migration and invasion by regulating hsa_circ_0000732 targeting miR-1184. The special role of ERß2 in TNBC may be the breakthrough of a targeted treatment strategy for TNBC.

Circular RNA circSNX6 promotes sunitinib resistance in renal cell carcinoma through the miR-1184/GPCPD1/ lysophosphatidic acid axis.

Sunitinib resistance is a major challenge in systemic therapy for renal cell carcinoma (RCC). The role of circular RNAs (circRNAs) in regulating sunitinib resistance of RCC is largely unknown. We established sunitinib-resistant RCC cell lines in vivo. Through RNA-sequencing, we identified circSNX6, whose expression is upregulated in sunitinib-resistant cells compared with their parental cells. High circSNX6 expression was correlated with sunitinib resistance and worse oncologic outcomes in a cohort of 81 RCC patients. In vitro and in vivo experiments confirmed that circSNX6 could promote sunitinib resistance in RCC. circSNX6 acts as a molecular "sponge" to relieve the suppressive effect of microRNA (miR)-1184 on its target gene, glycerophosphocholine phosphodiesterase 1 (GPCPD1), which increases intracellular lysophosphatidic acid (LPA) levels and, ultimately, promotes sunitinib resistance in RCC cells. Our findings demonstrated that the circSNX6/miR-1184/GPCPD1 axis had a critical role in regulation of intracellular LPA levels and sunitinib resistance in RCC; they also provide a novel prognostic indicator and promising therapeutic targets.

Circular RNA hsa_circ_0001598 promotes programmed death-ligand-1-mediated immune escape and trastuzumab resistance via sponging miR-1184 in breast cancer cells.

Approximately 25% of breast cancer (BC) patients are HER2-positive. Trastuzumab is used as a targeted therapy drug to treat HER2-positive BC patients; however, the drug resistance remains a big challenge. Circular RNAs (circRNAs) are reported to be involved in drug resistance, but the role of circ_0001598 has never been studied in BC. First, we identified the expression of circ_0001598 by RT-qPCR in BC. The gain-of-function and loss-of-function studies were applied to study the functional roles of circ_0001598 and its target gene. We observed upregulation of circ_0001598 in BC tissues, especially in trastuzumab-resistant BC samples. We further identified that miR-1184 is a functional target of circ_0001598. Moreover, it was found that programmed death-ligand 1 (PD-L1) was a direct target of miR-1184. The oncogenic effects of circ_0001598 in promoting BC cell growth, trastuzumab-resistance, PD-L1 expression, and escaping of CD8 T cell killing were abolished after the restoration of miR-1184. In conclusion, we demonstrate that circ_0001598/miR-1184/PD-L1 signaling plays a crucial role in the regulation of BC progression and trastuzumab-resistance phonotypes, which suggests that circ_0001598 may be a molecular target to treat HER2-positive BC patients.

CircCA12 Promotes Malignant Process via Sponging miR-1184 and Upregulating RAS Family in Bladder Cancer.

Circular RNAs (circRNAs) are a panel of non-coding RNAs that mediate the regulation of gene expression, as well as pathological responses. Nonetheless, the function and expression pattern of circRNAs in urinary bladder cancer (UBC) remain unclear. Herein, we examined the function of circCA12 in UBC development. qRT-PCR results demonstrated remarkable circCA12 upregulation in UBC cell lines, as well as tissues. CCK-8, colony formation, and xenograft assays were employed to determine the effect of circCA12 on UBC. Our data illustrated silencing circCA12 repressed the proliferation along with the colony-formation capability of UBC cells. The migration and metastasis potential of UBC cells were remarkably abated in vivo, as well as in vitro after transfection with si-cirCA12 or sh-circCA12. Moreover, luciferase reporter and RIP assays indicated that circCA12 binds to miRNA-1184 through sponging miRNA, thereby up-regulating the expression of RAS family genes (NRAS, KRAS, and HRAS). In conclusion, the circCA12/miRNA-1184/RAS family was identified as a regulatory axis in UBC progression.

Knockdown of circROBO2 attenuates acute myocardial infarction through regulating the miR-1184/TRADD axis.

BACKGROUND: Studies have found that circular RNAs (circRNAs) play key roles in cardiovascular diseases. However, the function of circROBO2 in acute myocardial infarction (AMI) is unclear. This study aimed to investigate the pathogenesis of circROBO2 in AMI. METHODS: qRT-PCR and Western blot were used to determine the expression levels of circROBO2, miR-1184, and TRADD in AMI and sham-operated mouse models at mRNA and protein level, respectively. The relationship among miR-1184, circROBO2 and TRADD was evaluated by RNA immunoprecipitation (RIP) analysis and luciferase reporter gene analysis. The roles of circROBO2, miR-1184, and TRADD in myocardial cell apoptosis were evaluated using flow cytometry. Ultrasound echocardiography, serum creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH), myocardial infarction area, and myocardial cell apoptosis were measured to examine the effects of circROBO2 on myocardial injury. RESULTS: The expression levels of miR-1184 were significantly reduced, and the expression levels of circROBO2 and TRADD were significantly increased in MI group. CircROBO2 acted as a sponge for miR-1184 by upregulating the expression of TRADD. In addition, overexpression of miR-1184 enhanced the protective effect of knockdown of circROBO2 by partially inhibiting the expression of TRADD in vivo and in vitro. CONCLUSION: Knockdown of circROBO2 reduced the apoptosis of cardiomyocytes by increasing the expression levels of miR-1184, which in turn decreased the expression levels of TRADD in the myocardium post-MI.

Interference with circBC048201 inhibits the proliferation, migration, and invasion of bladder cancer cells through the miR-1184/ITGA3 axis.

The abnormal expression of circular RNA (circRNA) is bound up with the progress of various human cancers. This study aimed to reveal the potential role and mechanism of circBC048201 in the proliferation, migration, and invasion of bladder cancer cells. Quantitative real-time PCR was performed to detect the expression of circBC048201. Cell Counting Kit-8, colony formation, and transwell migration and invasion assays were used to confirm the in vitro functions of circBC048201. Western blot, RNA pull-down, and dual-luciferase reporter gene experiments were performed to study the potential mechanism. circBC048201 was abnormally highly expressed in bladder cancer tissues and cells, and the interference with circBC048201 inhibited bladder cancer cell proliferation, migration, and invasion. From the potential mechanism analysis, our data suggested that circBC048201 and miR-1184, miR-1184 and ITGA3 could bind to each other, and the interference with circBC048201 repressed bladder cancer cell proliferation, migration, and invasion through the miR-1184/ITGA3 axis. In summary, our results showed that circBC048201 was abnormally highly expressed in bladder cancer tissues and cells, and the interference with circBC048201 inhibited the proliferation, migration, and invasion of bladder cancer cells through the miR-1184/ITGA3 axis.

Hsa_circ_0128846 promotes tumorigenesis of colorectal cancer by sponging hsa-miR-1184 and releasing AJUBA and inactivating Hippo/YAP signalling.

Hsa_circ_0128846 was found to be the most significantly up-regulated circRNA in our bioinformatics analysis. However, the role of hsa_circ_0128846 in colorectal cancer has not been explored. We thus aim to explore the influence and mechanism of hsa_circ_0128846 in colorectal cancer by sponging its downstream miRNA target miR-1184. We collected 40 colorectal cancer patients' tumour tissues to analyse the expression of hsa_circ_0128846, miR-1184 and AJUBA using qRT-PCR and Western blot where needed. Then, we constructed stably transfected SW480 and HCT116 cells to study the influence of hsa_circ_0128846, miR-1184 and AJUBA on colorectal cancer cell phenotypes. To obtain reliable results, a plethora of experiments including RNA immunoprecipitation assay, flow cytometry, EdU incorporation assay, wound healing migration assay, transwell invasion assay and live imaging of nude mice xenograft assay were performed. The binding relationship between hsa_circ_0128846, miR-1184 and AJUBA mRNA in colorectal cancer was validated by reported gene assay. In colorectal cancer tissues, circ_0128846 and AJUBA were both significantly up-regulated, while miR-1184 was significantly down-regulated compared with healthy tissues. Meanwhile, hsa_circ_0128846 can absorb miR-1184 to promote the progression of CRC in vivo and SW480 and HCT116 cell phenotypes in vitro. The knockdown of AJUBA, a downstream target of miR-1184, reversed the effect of miR-1184 in CRC cells via enhancing the phosphorylation of the Hippo/YAP signalling pathway proteins MST1, LATS1 and YAP. This study revealed that hsa_circ_0128846 contributed to the development of CRC by decreasing the expression of miR-1184, thereby increasing AJUBA expression and inactivating Hippo/YAP signalling.

miR-1184 regulates the proliferation and apoptosis of colon cancer cells via targeting CSNK2A1.

MicroRNA (miRNA) exerts an important part in colon cancer cell proliferation and apoptosis. Meanwhile, the dysregulation of some miRNAs is detected in colon cancer cells. However, it remains unclear about the underlying mechanism of their effects on tumor pathogenesis. The current work aimed to examine the miR-1184 effect on colon cancer cells. The differentially expressed miRNAs (DEMs), including miR-9-3p, miR-1184, miR-492, miR-92a-1-5p and miR-20a-3p, were obtained from the GSE115108 and GSE132619 data sets using the 'GEO2R' online tool. Based on the findings, miR-1184 was significantly down-regulated within colon cancer cells and tissues. Moreover, the experimental results of CCK8, flow cytometry, colony formation and Western blotting assays showed that, miR-1184 over-expression suppressed colon cancer cell proliferation through inhibiting Ki67 expression and promoted their apoptosis through up-regulating cleaved caspase-3 and down-regulating Bcl-2 expression. By contrast, miR-1184 inhibition exerted the opposite effects. A total of 110 target genes of miR-1184 were predicted using the TargetScan and miRTarBase databases, which were then used to construct the protein-protein interaction (PPI) network based on the DAVID and STRING websites and to perform GO and KEGG pathway enrichment analyses. The MCODE plug-in of cytoscape was utilized to verify that CSNK2A1 was the target gene and key gene in significant modules. MiR-1184 directly targets CSNK2A1 via using RNA immunoprecipitation assay and luciferase reporter gene assay. According to the results, CSNK2A1 over-expression reversed the functions of miR-1184 over-expression in suppressing colon cancer cell proliferation and enhancing their apoptosis. In conclusion, over-expression of miR-1184 inhibits colon cancer cell proliferation but promotes their apoptosis through down-regulating CSNK2A1 expression.