CircRNA circPDSS1 promotes the gastric cancer progression by sponging miR-186-5p and modulating NEK2

The aim of this study is to investigate the regulatory mechanism of circPDSS1/miR-186-5p/NEK2 axis on the viability and proliferation in gastric cancer (GC) cell line. Differentially expressed circRNAs, miRNAs, and mRNAs in GC tissues and paracarcinoma tissues were analyzed using gene chips GSE83521, GSE89143, and GSE93415. Then, the expression of circPDSS1, miR-186-5p, and NEK2 was analyzed via quantitative real-time polymerase chain reaction (qRT-PCR). Survival analysis was adopted to explore the association between the circPDSS1 expression and the prognosis of GC. The effect of circPDSS1 on GC cell cycle and apoptosis was verified with the flow cytometry. Targeting relationships among circPDSS1, miR-186-5p, and NEK2 were predicted via bioinformatics analysis and demonstrated by the dual-luciferase reporter assay. Our results showed that circPDSS1 and NEK2 were high-expressed whereas miR-186-5p was low-expressed in GC tissues and cells. CircPDSS1 promoted GC cell cycle and inhibited apoptosis by sponging miR-186-5p, while miR-186-5p inhibited cell cycle and promoted apoptosis by targeting NEK2. Thus, circPDSS1 acts as a tumor promoter by regulating miR-186-5p and NEK2, which could be a potential biomarker and therapeutic target for the management of GC.     

Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p

Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p–SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p–SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.Subject terms: Gastrointestinal cancer, Non-coding RNAs     

Circ_0003159 upregulates LIFR expression through competitively binding to miR-221-3p/miR-222-3p to block gastric cancer development

Journal of Molecular Histology - Gastric cancer (GC) remains a major cause of cancer-related deaths. Increasing studies suggest that cancer development is accompanied by the deregulation of...     

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.     

LncRNA DANCR promotes cervical cancer progression by upregulating ROCK1 via sponging miR-335-5p

Emerging evidence highlights the key regulatory roles of long noncoding RNAs (lncRNAs) in the initiation and progression of numerous malignancies. The lncRNA identified as differentiation antagonizing nonprotein coding RNA (DANCR) is a novel lncRNA widely involved in the development of multiple human cancers. However, the function of DANCR and its potential molecular mechanism in cervical cancer remain unclear. In this study, we discovered that DANCR was significantly elevated in cervical cancer tissues and cells, and was closely correlated with poor prognosis of cervical cancer patients. In addition, knockdown of DANCR inhibited proliferation, migration, and invasion of cervical cancer cells in vitro, indicating that DANCR functioned as an oncogene in cervical cancer. Moreover, we verified that DANCR could directly bind to miR-335-5p, isolating miR-335-5p from its target gene Rho-associated coiled-coil containing protein kinase 1 (ROCK1). Functional analysis showed that DANCR regulated ROCK1 expression by competitively binding to miR-335-5p. Further cellular behavioral experiments revealed that miR-335-5p mimics and ROCK1 knockdown reversed the effects of upregulated DANCR on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells by rescue assays. In summary, this study demonstrated that DANCR promoted cervical cancer progression by functioning as a competing endogenous RNA (ceRNA) to regulate ROCK1 expression via sponging miR-335-5p, suggesting a novel potential therapeutic target for cervical cancer.     

Hsa_circRNA_0088036 acts as a ceRNA to promote bladder cancer progression by sponging miR-140-3p

Circular RNAs (circRNAs) are a class of non-coding RNAs that play vital roles in cancer biology. However, the potential role of hsa_circRNA_0088036 in bladder cancer (BCa) remains unknown. Hsa_circRNA_0088036 was identified by microarray analysis and validated by quantitative real-time polymerase chain reaction. Functional assays were conducted to confirm the effects of hsa_circRNA_0088036 on the growth, migration, invasion, tumorigenesis, and metastasis of BCa cells. The luciferase reporter assay and RNA pull down assay were performed to investigate the interactions between hsa_circRNA_0088036, miR-140-3p, and forkhead box protein Q1 (FOXQ1). Upregulated expression of hsa_circRNA_0088036 in BCa tissues and cell lines was positively correlated with overall survival and clinicopathologic characteristics. Knockdown of hsa_circRNA_0088036 inhibited the growth, migration, and invasion of BCa cells both in vivo and in vitro. Mechanistically, hsa_circRNA_0088036 could directly interact with miR-140-3p and act as a miRNA sponge to modulate FOXQ1 expression. Knockdown of hsa_circRNA_0088036 inhibited the proliferation, migration, and metastasis of BCa cells via miR-140-3p/FOXQ1 signaling, suggesting that hsa_circRNA_0088036 is a potential biomarker and therapeutic target for BCa.Subject terms: Bladder cancer, Long non-coding RNAs     

Circ_002059 suppresses cell proliferation and migration of gastric cancer via miR-182/MTSS1 axis

Circular RNAs (circRNAs) play either oncogenic or tumor suppressive roles in gastric cancer (GC).A previous study demonstrated that circ_002059,a typical circRN...     

Circ_0001093 promotes glutamine metabolism and cancer progression of esophageal squamous cell carcinoma by targeting miR-579-3p/glutaminase axis

Journal of Bioenergetics and Biomembranes - Increasing studies indicate that circular RNAs (circRNAs) play critical roles in tumor metabolism of multiple cancers. However, the contribution of...     

Circ_0120175 promotes laryngeal squamous cell carcinoma development through up-regulating SLC7A11 by sponging miR-330-3p

Journal of Molecular Histology - The aim of our study was to illustrate the role of circular RNA 0120175 (circ_0120175) and its associated mechanism in laryngeal squamous cell carcinoma (LSCC)...     

LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p

Up to date, the mechanism of gastric cancer (GC) development is poorly understood. This study was to demonstrate the effects of LINC00339 on GC progression. Here, we found that LINC00339 was overexpressed expressed in GC tissues and predicted poor outcome. By CCK8, colony formation and Transwell assays, we showed LINC00339 knockdown suppressed GC cell proliferation, migration, and invasion in vitro. Flow cytometry analysis (FACS) indicated that LINC00339 knockdown induced tumor cell apoptosis. Besides, we utilized the xenograft assay and found that LINC00339 depletion led to decreased tumor growth in vivo. Mechanistically, miR-377-3p was found to be inhibited by LINC00339. And LINC00339 suppressed miR-377-3p to upregulate DCP1A, which consequently promoted GC progression. In conclusion, LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p.     

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.