Circ_0011385 knockdown inhibits cell proliferation, migration and invasion, whereas promotes cell apoptosis by regulating miR-330-3p/MYO6 axis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor. Recent studies have showed circular RNA (circRNA) participates in the development of CRC. The study was designed to reveal the role of circ_0011385 in CRC progression and underneath mechanism. METHODS: The expression circ_0011385, microRNA-330-3p (miR-330-3p) and myosin VI (MYO6) mRNA were determined by quantitative real-time polymerase chain reaction. Protein expression was detected by Western blot assay. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), cell colony formation and flow cytometry assays. Cell apoptosis was demonstrated by flow cytometry analysis. Cell migration and invasion were evaluated by wound-healing assay and transwell invasion assay, respectively. The binding sites between miR-330-3p and circ_0011385 or MYO6 were predicted by CircInteractome or starBase online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. RESULTS: Circ_0011385 and MYO6 expression were dramatically upregulated, while miR-330-3p expression was downregulated in CRC tissues or cells compared with control groups. Circ_0011385 expression was associated with tumor size, tumor-node-metastasis stage (TNM) stage and lymph node metastasis of CRC patients. Circ_0011385 silencing or MYO6 absence repressed cell proliferation, migration and invasion, whereas induced cell apoptosis in CRC. Additionally, miR-330-3p inhibitor or MYO6 overexpression attenuated the repressive impacts of circ_0011385 silencing on CRC process. Circ_0011385 was associated with miR-330-3p, and miR-330-3p targeted MYO6. Circ_0011385 knockdown inactivated MEK1/2/ERK1/2 signaling pathway by miR-330-3p/MYO6 axis. Furthermore, circ_0011385 knockdown suppressed tumor growth in vivo. CONCLUSION: Circ_0011385 regulated CRC process by miR-330-3p/MYO6 axis through MEK1/2/ERK1/2 signaling pathway, providing a novel therapeutic target for CRC.

Circular RNA hsa_circ_0011385 contributes to cervical cancer progression through sequestering miR-149-5p and increasing PRDX6 expression.

Cervical cancer (CC) is a common tumor in the female reproductive tract. Circular RNA hsa_circ_0011385 has been reported to be up-regulated in CC tissues. Nevertheless, the role and regulatory mechanism of hsa_circ_0011385 in CC are still being further verified. The levels of hsa_circ_0011385, microRNA (miR)- 149-5p, and peroxiredoxin 6 (PRDX6) mRNA in CC samples and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to survey the impacts of hsa_circ_0011385 inhibition on CC cell proliferation, colony formation, cycle progression, apoptosis, metastasis, invasion, and angiogenesis. Protein levels were detected by western blotting. The relationship between hsa_circ_0011385 or PRDX6 and miR-149-5p was verified by dual-luciferase reporter, RNA immunoprecipitation (RIP), and/or RNA pull-down assays. The tumorigenesis role of hsa_circ_0011385 in CC was confirmed by xenograft assay. We observed that hsa_circ_0011385 and PRDX6 were up-regulated while miR-149-5p was down-regulated in CC samples and cell lines. CC patients with high hsa_circ_0011385 expression possessed a shorter overall survival. Hsa_circ_0011385 knockdown reduced tumor growth in vivo and facilitated apoptosis, cell cycle arrest, impeded proliferation, metastasis, invasion, and angiogenesis of CC cells in vitro. Hsa_circ_0011385 could mediate PRDX6 expression through binding to miR-149-5p. MiR-149-5p silencing reversed hsa_circ_0011385 knockdown-mediated effects on CC cell angiogenesis and malignancy. PRDX6 overexpression overturned the inhibitory effects of miR-149-5p overexpression on angiogenesis and malignant behaviors of CC cells. In conclusion, hsa_circ_0011385 accelerated angiogenesis and malignant behaviors of CC cells by regulating the miR-149-5p/PRDX6 axis, manifesting that hsa_circ_0011385 might be a therapeutic target for CC.

Aloin decelerates the progression of hepatocellular carcinoma through circ_0011385/miR-149-5p/WT1 axis.

CircRNA/miRNA/mRNA axis has been reported to play crucial regulatory roles in multiple cancers, including hepatocellular carcinoma (HCC). In addition, recent investigations revealed that aloin exerted anti-tumor functions in HCC. However, the underlying mechanism of aloin on anti-tumor functions in HCC remained elusive. Therefore, this study aimed to investigate whether circRNA/miRNA/mRNA axis medicated the anti-tumor effect of aloin in HCC. Cell viability, invasion, apoptosis and autophagy were accessed by cell counting kit-8 (CCK-8), transwell invasion assay, flow cytometry, Western blot and immunofluorescence analysis, respectively. Expression levels of circ_0011385, miR-149-5p and WT1 mRNA were determined using qRT-PCR assay. Binding sites between miR-149-5p and circ_0011385 or WT1 were predicted in starBase database. The binding relationship among circ_0011385, miR-149-5p and WT1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation. Besides, the rescue experiments were performed by co-transfection with cric_0011385 overexpression plasmid, si-cric_0011385, miR-149-5p mimic and inhibitor, WT1 pDNA and si-WT1 in HCC cells. Furthermore, tumor growth was also investigated in the xenograft mouse model. Aloin inhibited HCC proliferation and invasion as well as promoted apoptosis and autophagy both in vitro and in vivo. Besides, aloin suppressed circ_0011385 expression. Overexpressed circ_0011385 partially reversed the anti-tumor effect of aloin on HCC. In addition, it was revealed that the circ_0011385, miR-149-5p and WT1 genes were abnormally expressed in HCC. Furthermore, the binding interactions between circ_0011385, miR-149-5p and WT1 were predicted and confirmed. Moreover, the effect of circ_0011385 on the anti-tumor role of aloin in HCC was rescued by miR-149-5p mimics. MiR-149-5p regulated HCC progression via modulating WT1. Aloin suppressed cell proliferation, invasion and tumor growth and promoted apoptosis and autophagy in HCC through regulating circ_0011385/miR-149-5p/WT1 axis. Aloin may be a potential candidate drug for HCC treatment.Abbrevations: HCC: Hepatocellular carcinoma; ceRNA: competing endogenous RNA; miRNA: microRNA; MREs: miRNA response elements; WT1: Wilms' tumor 1; MMP-2: Matrix metalloproteinase; EMT: epithelial-mesenchymal transition; GADPH: glyceraldehyde 3-phosphate dehydrogenase; WT: wild type; MUT: mutant type; DMEM: dulbecco's modified eagle medium.

Circular RNA circ_0011385 promotes cervical cancer progression through competitively binding to miR-149-5p and up-regulating SOX4 expression.

Circular RNAs (circRNAs), emerging as a new type of non-coding RNAs, play important roles in cancers. Instead, the functions and mechanisms of circ_0011385 in cervical cancer (CC) are still inconclusive. Microarray data GSE102686 was downloaded from Gene Expression Omnibus (GEO) database, and were utilized to screen out circRNAs differently expressed in CC tissues. Circ_0011385, miR-149-5p, SRY-box transcription factor 4 (SOX4) mRNA expressions in CC tissues and cells were probed by quantitative real-time PCR (qRT-PCR). CC cell lines with circ_0011385 knockdown were constructed, and he multiplication, migration, invasion, and apoptosis of CC cells were evaluated by cell counting kit-8 (CCK-8) method, transwell assay, and flow cytometry. In addition, the targeting relationships between miR-149-5p and circ_0011385 or SOX4 mRNA 3'UTR were probed by dual-luciferase reporter gene assay and RNA pull-down assay. The regulatory function of circ_0011385 and miR-149-5p on SOX4 expression was studied with western blot. Expressions of circ_0011385 and SOX4 mRNA were raised in CC tissues and cells, while miR-149-5p expression was decreased. Knocking down circ_0011385 restrained the multiplication, migration, and invasion of CC cells and induced the apoptosis. Circ_0011385 directly targeted miR-149-5p, and SOX4 was the target of miR-149-5p, which could be positively regulated by circ_0011385. Circ_0011385 elevates SOX4 expression by targeting miR-149-5p, thus participating in promoting the malignant biological behaviors of CC cells.

Hsa_circ_0011385 accelerates the progression of thyroid cancer by targeting miR-361-3p.

BACKGROUND: Thyroid cancer is an endocrine malignancy that is growing in incidence worldwide. Despite progress in diagnostics and treatment of thyroid cancer, prognosis remains poor. Emerging research has shown that circular RNAs (circRNAs) have crucial regulatory roles in cancers. However, the possible functions and mechanisms of hsa_circ_0011385 remain undetermined. MATERIALS AND METHODS: Expression levels of hsa_circ_0011385 and miR-361-3p were evaluated by qRT-PCR assay. The interaction between hsa_circ_0011385 and miR-361-3p was verified by dual-luciferase reporter assay. Effects of hsa_circ_0011385 or miR-361-3p on cell viability, proliferation, cell cycle, apoptosis, migration and invasion were confirmed by cell counting kit-8 (CCK-8), carboxyfluoresceinsuccinimidyl ester (CFSE), flow cytometry, and Transwell assays in vitro. The effect of hsa_circ_0011385 on thyroid cancer progression was also determined by in vivo tumor formation assay. Target genes of miR-361-3p were predicted by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and the expression of apoptosis- and metastasis-related proteins were assessed by Western blot assay. RESULTS: Hsa_circ_0011385 upregulated in thyroid cancer; hsa_circ_0011385 knockdown inhibited thyroid cancer cell proliferation, migration and invasion, and promoted cell cycle arrest and apoptosis. In addition, hsa_circ_0011385 could negatively regulate miR-361-3p by functioning as a sponge. Hsa_circ_0011385 promoted thyroid cancer cell proliferation, migration and invasion and suppressed cell cycle arrest and apoptosis by targeting miR-361-3p in vitro. We also found that hsa_circ_0011385 knockdown dramatically inhibited thyroid cancer growth in vivo. Furthermore, hsa_circ_0011385 regulated expression of apoptosis and metastasis-related proteins in thyroid cancer. CONCLUSIONS: Hsa_circ_0011385facilitated thyroid cancer cell proliferation, invasion and migration, and inhibited thyroid cancer cell cycle arrest and apoptosis by targeting miR-361-3p, suggesting that the hsa_circ_0011385/miR-361-3p axis might be a promising therapeutic target for thyroid cancer.