Circular RNA ITCH attenuates the progression of nasopharyngeal carcinoma by inducing PTEN upregulation via miR-214.

Circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH) has previously been reported to play a key role in carcinogenesis. Nevertheless, the role of circ-ITCH in nasopharyngeal carcinoma (NPC) remains to be explored. Gene expression analysis was performed using a quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. The role of circ-ITCH in NPC was explored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, colony formation, transwell invasion, scratch healing and xenograft tumor assays. Furthermore, luciferase reporter assay was carried out to assess the interactions among circ-ITCH, microRNA-214 (miR-214) and phosphatase and tensin homolog (PTEN). The levels of circ-ITCH and PTEN were decreased, whereas the level of miR-214 was increased in NPC tissues collected from 28 subjects compared to normal nasopharynx tissues collected from 15 subjects. Moreover, a negative correlation between circ-ITCH and miR-214 expression and a positive correlation between circ-ITCH and PTEN expression were observed in NPC tissues. Downregulation of circ-ITCH expression was also observed in NPC cell lines. In addition, upregulation of circ-ITCH markedly inhibited NPC cell proliferation, migration and invasion. Furthermore, circ-ITCH was confirmed to exert its function by sponging miR-214. PTEN was found to be a direct target gene of miR-214 and its expression was negatively correlated with miR-214 expression in NPC tissues. Moreover, our results showed that the circ-ITCH/miR-214 axis regulated NPC proliferation, migration and invasion through regulating the expression of PTEN. Upregulation of circ-ITCH or PTEN blocked miR-214-mediated promotion of NPC tumorigenesis in vitro. Additionally, upregulation of circ-ITCH also suppressed NPC tumorigenesis in vivo. The present study demonstrated that circ-ITCH suppressed NPC tumorigenesis by upregulating PTEN expression through interacting with miR-214, thus proposing a novel mechanism for NPC inhibition.

Wang L ，Sang J ，Zhang Y ，Gao L ，Zhao D ，Cao H ... -  《-》

Hsa_circ_0000345 inhibits cell proliferation, migration and invasion of nasopharyngeal carcinoma cells via miR-513a-3p/PTEN axis.

Hsa_circ_0000345 has been reported to be down-regulated in nasopharyngeal carcinoma (NPC). Whether hsa_circ_0000345 can exert antitumor effect in NPC remains unclear. This study aimed to investigate the possible biological role of hsa_cic_0000345 in suppressing the progression of NPC. Hsa_circ_0000345 expression was detected in normal nasopharynx epithelial cells (NP69) and NPC cell lines (SUNE1, HONE1, 6-10B and HNE1). The influence of hsa_circ_0000345 on cell proliferation, migration and invasion of NPC cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays. Quantitative real-time PCR and western blot were performed to examine gene and protein expression, respectively. Luciferase reporter assay was carried out to verify the relationship among hsa_circ_0000345, miR-513a-3p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Compared with NP69 cells, hsa_circ_0000345 was down-regulated in NPC cells. Moreover, hsa_circ_0000345 overexpression repressed cell proliferation, migration and invasion of SUNE1 cells, whereas hsa_circ_0000345 knockdown promoted cell proliferation, migration and invasion of 6-10B cells. Furthermore, hsa_circ_0000345 promoted PTEN expression by sponging miR-513a-3p. Both miR-513a-3p overexpression and PTEN knockdown promoted cell proliferation, migration and invasion of SUNE1 cells, which were effectively abolished by hsa_circ_0000345 up-regulation. Hsa_circ_0000345 inhibits cell proliferation, migration and invasion of NPC cells via miR-513a-3p/PTEN axis, thereby suppressing the progression of NPC. Thus, this work suggests that hsa_circ_0000345 may be a potential biomarker for diagnosis and treatment of NPC.

Jiang C ，Li H ，Liu F ，Shi L ，Liu J ，Li Y ... -  《-》

Circular RNA circ-ITCH inhibits bladder cancer progression by sponging miR-17/miR-224 and regulating p21, PTEN expression.

Yang C ，Yuan W ，Yang X ，Li P ，Wang J ，Han J ，Tao J ，Li P ，Yang H ，Lv Q ，Zhang W ... -  《-》

Circular RNA Hsa_circ_0066755 as an Oncogene via sponging miR-651 and as a Promising Diagnostic Biomarker for Nasopharyngeal Carcinoma.

Background: Circular RNAs (circRNAs) represent a class of broad and diversified endogenous RNAs that regulate gene expressions in eukaryotes. Hsa_circ_006675 has been proven as an important circRNA molecule in nasopharyngeal carcinoma (NPC), however, its function still remains elusive. This study aims to discuss the biofunctions of hsa_circ_0066755 in NPC. Methods: We detected the expression levels of hsa_circ_0066755 in NPC patients by quantitative real-time polymerase chain reaction (qRT-PCR), and the corresponding ROC curves were plotted. Functional experiments including CCK-8, colony formation, Transwell assay and Xenograft experiment were conducted. Bioinformatics analysis was performed to seek miRNAs which might have binding sites with hsa_circ_0066755. Luciferase reporter assays were finally carried out to verify the binding sites. Results: We found significant increases of hsa_circ_0066755 in the plasma and tissues of the patients. Moreover, its levels were positively correlated with clinical staging (P=0.019). The receiver operating characteristic (ROC) analysis showed that the area under the curves (AUCs) of tissue and plasma hsa_circ_0066755 for distinguishing NPC from non-cancerous controls were 0.8537 and 0.9044, respectively. Both tissue and plasma hsa_circ_0066755 testing presented a comparable diagnostic accuracy to the magnetic resonance imaging (MRI). Our in-vitro experiment showed that the overexpression of hsa_circ_0066755 facilitated the growth, proliferation, clone formation, invasion and migration of CNE-1 NPC cells, while its down-regulation showed completely opposite effects. The xenograft experiment showed that exogenous hsa_circ_0066755 could significantly enhance the in-vivo tumorigenic ability of CNE-1 cells. Rescue assay further confirmed hsa_circ_0066755 as a tumor facilitator by sponging miR-651. Conclusions: Collectively, this study reported for the first time that hsa_circ_0066755 played a role of oncogene in NPC and could be used as an effective diagnostic marker for NPC, and that hsa_circ_0066755 / miR-651 axis also involved in the progression of NPC.

Wang J ，Kong J ，Nie Z ，Chen D ，Qiang J ，Gao W ，Chen X ... -  《International Journal of Medical Sciences》

Hsa_circ_0081534 facilitates malignant phenotypes by sequestering miR-874-3p and upregulating FMNL3 in nasopharyngeal carcinoma.

Circular RNAs (circRNAs) are connected to nasopharyngeal carcinoma (NPC) development and progression. CircRNA hsa_circ_0081534 (circ_0081534) has been reported to be associated with NPC progression, but its underlying regulatory mechanisms are largely unknown. Thus, the study aims to investigate the mechanism by which circ_0081534 regulates NPC progression. Quantitative reverse transcription polymerase chain reaction was conducted to detect circ_0081534 expression. Loss-of-function assays were conducted to evaluate the role of circ_0081534, including 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU) staining, colony formation, flow cytometry, transwell, western blotting, and xenograft assays. Targeting relationship was identified through dual-luciferase reporter assay and RNA immunoprecipitation. Our data exhibited that circ_0081534 was upregulated in NPC samples and cells. Knockdown of circ_0081534 repressed NPC cell proliferation, migration, invasion, EMT, and triggered NPC cell apoptosis. Also, circ_0081534 silencing decreased NPC cell growth in xenograft models. Circ_0081534 functioned as a miR-874-3p sponge, and downregulation of miR-874-3p alleviated the suppressive effects of circ_0081534 silencing on NPC cell malignant phenotypes. MiR-874-3p targeted FMNL3, and circ_0081534 regulated FMNL3 expression through serving as a miR-874-3p sponge. Upregulation of FMNL3 relieved the inhibitory effects of circ_0081534 downregulation on NPC cell malignant phenotypes. circ_0081534 interference repressed NPC progression partly by modulating the miR-874-3p/FMNL3 axis.

He J ，Chen S ，Wu X ，Jiang D ，Li R ，Mao Z ... -  《-》