Circ-RNF111 Promotes Proliferation of Ovarian Cancer Cell SKOV-3 by Targeting the MiR-556-5p/CCND1 Axis.

The aim of this study was to investigate the role and mechanism of circ-RNF111 in the human ovarian cancer cell line SKOV-3. First, qRT-PCR was used to detect circ-RNF111 and miR-556-5p expression levels in human normal ovarian epithelial cells IOSE80 and human ovarian cancer cells SKOV-3. CCK-8 and colony formation assays were adopted to determine the proliferation rate and cell viability of SKOV-3 cells, respectively. Additionally, in an attempt to reveal the mechanism of circ-RNF111, we predicted the targeting relationship between miR-556-5p and circ-RNF111 as well as miR-556-5p and CCND1 using the circinteractome and TargetScan databases, respectively, and validated their relationship by dual-luciferase reporter assay. The protein expression levels of CCND1 in SKOV-3 cells were detected by Western blot. Based on the above experiments, the expression of circ-RNF111 was found to be up-regulated in SKOV-3, and the knockdown of circ-RNF111 significantly inhibited the proliferation and viability of SKOV-3 cells. Then we confirmed that circ-RNF111 sponged miR-556-5p in SKOV-3 cells to up-regulate CCND1 expression. In addition, simultaneous inhibition of miR-556-5p or overexpression of CCND1 in SKOV-3 cells with knockdown of circ-RNF111 reversed the inhibitory effect of knockdown of circ-RNF111 on the protein expression level of CCND1, cell proliferation rate, and cell viability. In summary, circ-RNF111 promotes the proliferation of SKOV-3 cells by targeting the miR-556-5p/CCND1 axis. Circ-RNF111 may serve as a potential target for ovarian cancer therapy.

Zuo L ，Tan Y ，Xu QL ，Li XL ，Xiao M ... -  《-》

Circ-RNF111 contributes to paclitaxel resistance in breast cancer by elevating E2F3 expression via miR-140-5p.

Circular RNAs (circRNAs) have been demonstrated to act as key regulators in the chemoresistance of human cancers, including breast cancer (BC). Here, we aimed to explore the role of circ-RNF111 in paclitaxel (PTX) resistance of BC. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of circ-RNF111, microRNA-140-5p (miR-140-5p) and E2F transcription factor 3 (E2F3) mRNA. The half maximal inhibitory concentration (IC50 ) of PTX, cell viability, colony formation and cell invasion were assessed by cell counting kit-8 (CCK-8) assay, colony formation assay and transwell assay, respectively. Glucose consumption and lactate production were determined by specific kits. A murine xenograft model was established to investigate the role of circ-RNF111 in PTX resistance of BC in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the relationship between miR-140-5p and circ-RNF111 or E2F3. Western blot assay was conducted to examine the protein level of E2F3. Circ-RNF111 was upregulated in PTX-resistant BC tissues and cells. Circ-RNF111 knockdown restrained IC50 of PTX, cell viability, colony numbers, cell invasion and glycolysis in PTX-resistant BC cells in vitro and enhanced PTX sensitivity in vivo. MiR-140-5p was a target of circ-RNF111 and miR-140-5p expression was negatively correlated with circ-RNF111 expression in BC tissues. The effect of circ-RNF111 knockdown on PTX resistance was rescued by miR-140-5p deletion. Additionally, miR-140-5p could interact with E2F3 and negatively regulate E2F3 expression. Moreover, miR-140-5p suppressed IC50 of PTX, cell viability, colony numbers, cell invasion and glycolysis by targeting E2F3. Circ-RNF111 improved PTX resistance of BC by upregulating E2F3 via sponging miR-140-5p.

Zang H ，Li Y ，Zhang X ，Huang G ... -  《-》

Hsa_circ_0008092 Contributes to Cell Proliferation and Metastasis in Hepatocellular Carcinoma via the miR-502-5p/CCND1 Axis.

The present study was targeted at investigating the effects of hsa_circRNA_0008092 (circ_0008092) on hepatocellular carcinoma (HCC) cell proliferation, migration, invasion and apoptosis, and its related mechanism. The gene expression profiles of GSE166678 were downloaded from the Gene Expression Omnibus database, and differentially expressed circRNAs in human HCC were screened out. Besides, circ_0008092, microRNA-502-5p (miR-502-5p) and cyclin D1 (CCND1) expressions in HCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRTPCR). Cell countering kit-8 (CCK-8), Transwell and flow cytometry assays were used to detect the proliferation, migration, invasion and apoptosis of HCC cells. Bioinformatics was utilized to predict the targeted relationships between miR-502-5p and circ_0008092, as well as miR-502-5p and CCND1 mRNA 3'-untranslated region (3'UTR). Western blot assay was applied to detect CCND1 protein expression in HCC cells. Circ_0008092 was highly expressed in HCC tissues and cells, which was associated with a shorter survival time in patients with HCC. Circ_0008092 overexpression promoted proliferation, migration and invasion, and inhibited apoptosis of HCC cells; circ_0008092 knockdown worked oppositely. Circ_0008092 directly targeted miR-502-5p and negatively modulated miR-502-5p expression. CCND1 Conclusion: Our data suggest that circ_0008092 promotes HCC progression by regulating the miR- 502-5p/CCND1 axis.

Maimaiti Y ，Kamali A ，Yang P ，Zhong K ，Abuduhadeer X ... -  《-》

Circ_0078607 inhibits the progression of ovarian cancer via regulating the miR-32-5p/SIK1 network.

Circular RNA (circRNA) has been shown to be involved in the regulation of human disease progression, including ovarian cancer (OC). Circ_0078607 was found to participate in OC progression. But its function and mechanism in OC deserve further exploration. The expression levels of circ_0078607, salt-inducible kinase 1 (SIK1) and microRNA (miR)-32-5p were examined by qRT-PCR. And the protein expression levels of SIK1, metastasis marker and apoptosis marker were determined using western blot analysis. EDU staining, colony formation assay, transwell assay and flow cytometry were used to detect the proliferation, migration, invasion and apoptosis of cells. Moreover, dual-luciferase reporter assay was employed to verify the interaction between miR-32-5p and circ_0078607 or SIK1. Xenograft models were constructed to perform in vivo experiments. Circ_0078607 and SIK1 were downregulated in OC tissues and cells. Overexpressed circ_0078607 and SIK1 could inhibit OC cell proliferation, migration, invasion, and promote apoptosis. MiR-32-5p could be sponged by circ_0078607, and its overexpression could reverse the suppressive effect of circ_0078607 on OC progression. Furthermore, SIK1 was a target of miR-32-5p, and circ_0078607 could regulate SIK1 by sponging miR-32-5p. The inhibitory effect of circ_0078607 on OC progression also could be reversed by SIK1 silencing. In vivo experiments showed that circ_0078607 reduced OC tumorigenesis by regulating the miR-32-5p/SIK1 axis. Circ_0078607 could serve as a sponge of miR-32-5p to regulate SIK1 expression, thereby inhibiting OC progression.

Jin Y ，Wang H 《-》

Hsa_circ_0079557 Promotes the Proliferation of Colorectal Cancer Cells Through the hsa_circ_0079557/miR-502-5p/CCND1 Axis.

Yu C ，Huang X ，Huang R ，Wang P ，Cai Z ，Guo Z ，Lan Q ，Cao H ，Yu J ... -  《-》