CircDUS2L (circ_0039908) promotes lung adenocarcinoma progression by upregulating PGAM1 by acting as a miR-590-5p molecular sponge

Lung adenocarcinoma (LUAD) is usually found at the metastatic stage. Circular RNA dihydrouridine synthase 2-like (DUS2L) (circDUS2L) has been discovered to be upregulated in LUAD. Nevertheless, the function of circDUS2L in LUAD has not been verified. Levels of circDUS2L, microRNA-590-5p (miR-590-5p), and phosphoglycerate mutase 1 (PGAM1) mRNA were analyzed using quantitative real-time polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, metastasis, and invasion were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), colony formation, 5-ethynyl-2′-deoxyuridine (Edu), flow cytometry, and transwell assays. Protein levels were detected by western blotting. Cell glycolysis was analyzed by measuring cell glucose consumption, lactate production, and extracellular acidification rate (ECAR). The regulatory mechanism of circDUS2L in LUAD cells was analyzed by bioinformatics analysis, dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. Xenograft assay was conducted to confirm the function of circDUS2L in vivo. CircDUS2L was highly expressed in LUAD tissues and cells. CircDUS2L silencing constrained xenograft tumor growth in vivo. CircDUS2L knockdown induced apoptosis, repressed viability, colony formation, proliferation, metastasis, invasion, and glycolysis of LUAD cells in vitro by releasing miR-590-5p via functioning as a miR-590-5p sponge. MiR-590-5p was lowly expressed in LUAD tissues and cells, and miR-590-5p mimic curbed malignant behaviors and glycolysis of LUAD cells by targeting PGAM1. PGAM1 was overexpressed in LUAD tissues and cells, and circDUS2L sponged miR-590-5p to regulate PGAM1 expression. CircDUS2L elevated PGAM1 expression through functioning as a miR-590-5p sponge, thus driving malignant behaviors and glycolysis of LUAD cells.     

Linc00475 promotes the progression of glioma by regulating the miR-141-3p/YAP1 axis

Glioma is the most prevalent and lethal primary brain tumour. Abundant long non-coding RNAs ( lncRNAs) are aberrant and play crucial roles in the oncogenesis of glioma. The exact functions of linc00475 in glioma remain blurred. Here, we analysed the expression levels of linc00475 by qRT-PCR and discovered that linc00475 was up-regulated in glioma and predicted a poor prognosis in patients with glioma. Besides, inhibiting linc00475 restrained the progression of glioma in vitro and in vivo. Further experiments confirmed that linc00475 regulated the progression of glioma by acting as a sponge for miR-141-3p. Moreover, we detected the binding sites of linc00475 and miR-141-3p, the YAP1- 3′UTR and miR-141-3p by luciferase reporters. The rescue assays confirmed that inhibiting linc00475 restrained the progression of glioma through the miR-141-3p/YAP1 pathway. Collectively, our research demonstrates the key roles of linc00475 in glioma, which could be a promising therapeutic target.     

Silencing lncRNA DUXAP8 inhibits lung adenocarcinoma progression by targeting miR-26b-5p

Lung adenocarcinoma (LUAD), a common type of lung cancer, has become a popularly aggressive cancer. Long noncoding RNAs (lncRNAs) play a critical role in the pathogenesis of human cancers, while the function of double homeobox A pseudogene 8 (DUXAP8) in LUAD remains to be fully inquired. Therefore, our study was conducted to elucidate the DUXAP8 expression in LUAD and its mechanism on the biological features of LUAD cells. Loss-of-function experiments were performed to assess the function of DUXAP8 proliferation and apoptosis of H1975 and A549 cells. Functionally, silencing DUXAP8 inhibited proliferation and induced apoptosis of LUAD cells. Mechanistically, further correlation assay indicated a negative association between miR-26b-5p and DUXAP8 expression. Subsequently, we testified that DUXAP8 exerted its role in the progression and development of LUAD through targeting miR-26b-5p. In summary, our results elucidated that that DUXAP8 promoted tumor progression in LUAD by targeting miR-26b-5p, which provide a novel therapeutic target for diagnosis and therapy of LUAD.     

LBX2-AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR-455-5p and miR-491-5p sponging

LBX2-AS1 is a long non-coding RNA that facilitates the development of gastrointestinal cancers and lung cancer, but its participation in ovarian cancer development remained uninvestigated. Clinical data retrieved from TCGA ovarian cancer database and the clinography of 60 ovarian cancer patients who received anti-cancer treatment in our facility were analysed. The overall cell growth, colony formation, migration, invasion, apoptosis and tumour formation on nude mice of ovarian cancer cells were evaluated before and after lentiviral-based LBX2-AS1 knockdown. ENCORI platform was used to explore LBX2-AS1-interacting microRNAs and target genes of the candidate microRNAs. Luciferase reporter gene assay and RNA pulldown assay were used to verify the putative miRNA-RNA interactions. Ovarian cancer tissue specimens showed significant higher LBX2-AS1 expression levels that non-cancerous counterparts. High expression level of LBX2-AS1 was significantly associated with reduced overall survival of patients. LBX2-AS1 knockdown significantly down-regulated the cell growth, colony formation, migration, invasion and tumour formation capacity of ovarian cancer cells and increased their apoptosis in vitro. LBX2-AS1 interacts with and thus inhibits the function of miR-455-5p and miR-491-5p, both of which restrained the expression of E2F2 gene in ovarian cancer cells via mRNA targeting. Transfection of miRNA inhibitors of these two miRNAs or forced expression of E2F2 counteracted the effect of LBX2-AS1 knockdown on ovarian cancer cells. LBX2-AS1 was a novel cancer-promoting lncRNA in ovarian cancer. This lncRNA increased the cell growth, survival, migration, invasion and tumour formation of ovarian cancer cells by inhibiting miR-455-5p and miR-491-5p, thus liberating the expression of E2F2 cancer-promoting gene.     

Circ-TRIO promotes TNBC progression by regulating the miR-432-5p/CCDC58 axis

Numerous studies have shown that circRNAs are aberrantly expressed in various cancers and play a significant role in tumor progression. However, the molecular mechanisms of circRNAs in triple-negative breast cancer (TNBC) remain ambiguous. By intersecting throughput data and qRT-PCR results from tissues and cell lines, circ-TRIO was identified as a potential oncogenic regulator of TNBC. Moreover, circ-TRIO expression was detected in TNBC tissues and was correlated with the recurrence and prognosis of TNBC patients. The circular characteristics of circ-TRIO were verified by RNase R and CHX assays. Functionally, the knockdown of circ-TRIO inhibited the proliferation, migration and invasion of TNBC cells, while the overexpression of circ-TRIO resulted in the opposite impacts. Mechanistically, a dual luciferase reporter assay and RNA immunoprecipitation were performed and indicated that circ-TRIO could combine with miR-432-5p to regulate the expression of coiled-coil domain containing 58 (CCDC58). In summary, our study illustrates that circ-TRIO plays an important role in the progression of TNBC by regulating the miR-432-5p/CCDC58 axis, which could broaden our insight into the underlying mechanisms and provide a novel prognostic marker of TNBC in the clinic.Subject terms: Breast cancer, Cancer     

Circular RNA TUBA1C accelerates the progression of non-small-cell lung cancer by sponging miR-143-3p

Non-small-cell lung cancer (NSCLC) is one of the most common solid tumors and the leading cause of lung cancer-related fatality. Growing evidence has indicated that circular RNAs (circRNAs) play important roles in the progression of multiple human cancers. As a novel circRNA, very little research has focused on the function of circRNA TUBA1C (circTUBA1C) in cancer development, including NSCLC. In the present study, we found that the expression of circTUBA1C was significantly upregulated in NSCLC tissues. The loss-of function assays suggested that circTUBA1C deficiency notably hampered cell proliferation as well as accelerated cell apoptosis in NSCLC. In mechanism, we discovered that circTUBA1C could act as a sponge for miR-143-3p and then negatively regulate miR-143-3p. Moreover, rescue assays demonstrated that knockdown of miR-143-3p could reverse circTUBA1C silence-mediated effects on cell proliferation and apoptosis. Besides, we established a xenografted tumor model to investigate the function of circTUBA1C in vivo. The result illustrated that the decline of tumor growth resulted from circTUBA1C deficiency could be recovered by miR-143-3p knockdown. Taken together, these findings indicated the important role of circTUBA1C/miR-143-3p axis in NSCLC, which may provide a potential target for NSCLC therapy.     

miR-455-5p regulates atrial fibrillation by targeting suppressor of cytokines signaling 3

Journal of Physiology and Biochemistry - Atrial fibrillation (AF) is a condition that heart beats quaveringly or irregularly, which causes blood clots, heart failure, stroke, and other...     

Tanshinone I restrains osteosarcoma progression by regulating circ_0000376/miR-432-5p/BCL2 axis

Molecular and Cellular Biochemistry - Circular RNAs (circRNAs) have been identified as important regulators in cancer progression. Nevertheless, little is known about the biological function of...     

Long noncoding HOXA11-AS knockdown suppresses the progression of non-small cell lung cancer by regulating miR-3619-5p/SALL4 axis

Journal of Molecular Histology - Accumulating evidence suggested that many long noncoding RNAs (lncRNAs) were widely involved in the development and progression of non-small cell lung cancer...     

Circular RNA hsa_circ_0030018 acts as a sponge of miR-599 to aggravate esophageal carcinoma progression by regulating ENAH expression

Esophageal carcinoma (EC) bears one of the most rapid-growing incidences in cancers, which also has the highest mortality rate worldwide. Multiple studies have authenticated that circular RNAs (circRNAs) significantly work on the progression of cancers. circRNA hsa_circ_0030018 was also verified to exert functions on the development of glioma previously. Nevertheless, the biological function of hsa_circ_0030018 in EC has not been well elucidated yet. In the present study, the results displayed the expression of hsa_circ_0030018 was dramatically increased in EC cells. Inhibition of has_circ_0030018 suppressed cell proliferation, migration, and epithelial-mesenchymal transition (EMT) process in EC. Based on molecular mechanism assays, has_circ_0030018 served as a sponge of miR-599. Enabled homolog (ENAH), which exhibited high expression in EC cells, was confirmed to be a downstream target gene of miR-599. Additionally, has_circ_0030018 positively regulated ENAH expression while miR-599 negatively regulated ENAH expression. Finally, by employing rescue assays, ENAH deficiency partially counteracted the promoting function of miR-599 silence on cell proliferation, migration, and EMT process in EC cotransfected with sh- has_circ_0030018#1 cells. In conclusion, hsa_circ_0030018 acted as a sponge of miR-599 to aggravate EC progression by regulating ENAH expression. Therefore, hsa_circ_0030018 might serve as a promising biomarker and therapeutic target for EC.     

circEVI5 acts as a miR-4793-3p sponge to suppress the proliferation of gastric cancer

Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs (ncRNAs) with a covalently closed loop structure. Accumulating evidence shows that circRNAs play vital roles in the growth, metastasis, treatment and prognosis of various cancers. However, the detailed functions and underlying mechanisms of circEVI5 (hsa_circ_0013162) in gastric cancer (GC) remain undocumented. In this study, the expression levels and prognostic value of circEVI5 were validated in GC tissue samples by using qRT-PCR. circEVI5 was significantly downregulated in GC tissues and cells, and low circEVI5 expression was correlated with poor prognosis. Next, in vitro CCK-8 assay, EdU incorporation assay, PI staining cell cycle assay, and in vivo xenograft mouse models were conducted to assess the functions of circEVI5. Gain of function experiments indicated that circEVI5 could inhibit GC cell proliferation and retard the cell cycle. Moreover, bioinformatics prediction showed that circEVI5 binds to miR-4793-3p, while FOXO1 may be a target of miR-4793-3p. Pull-down assays, RNA immunoprecipitation (RIP) assays, luciferase assays, and western blot were used to confirm the interactions between circEVI5, miR-4793-3p, and FOXO1. Functional assays demonstrated that circEVI5 suppressed the proliferation of GC by sponging miR-4793-3p and increasing FOXO1 expression levels. In conclusion, our study demonstrated that circEVI5 can bind miR-4793-3p as a ceRNA to eliminate the negative regulation of FOXO1, therefore suppressing GC proliferation.Subject terms: Gastric cancer, Oncogenesis     

Porcine acellular dermal matrix accelerates wound healing through miR-124-3p.1 and miR-139-5p

Background aimsCutaneous wound management is a major health problem and imposes a huge economic burden worldwide. Previous studies have demonstrated that wound healing is a highly coordinated process including epithelialization, angiogenesis, remodeling and scarring. This progression requires self-renewal, preservation and repair properties of stem cells. However, our understanding of the detailed internal regulatory mechanism following injury and the means to accelerate wound healing are limited.MethodsOur previous research revealed that porcine acellular dermal matrix (ADM) effectively promotes wound healing and scar formation through epidermal stem cells (ESCs), and this process is relevant to the alteration of internal miRNA levels. In this study, we investigated the regulatory function of porcine ADM treatment on miRNAs in ESCs.ResultsWe report that the treatment of porcine ADM reduced the levels of miR-124-3p.1 and miR-139-5p in wounds. MiR-124-3p.1 and miR-139-5p inhibited the expression of JAG1 and Notch1, respectively, by directly targeting miRNAs in ESCs.ConclusionsThis work demonstrates that porcine ADM induced down-regulation of miR-124-3p.1/139-5p in wounds and up-regulation of JAG1/Notch1 in ESCs, thus enhancing cutaneous wound healing.