Circular RNA NEK6 contributes to the development of non-small-cell lung cancer by competitively binding with miR-382-5p to elevate BCAS2 expression at post-transcriptional level.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is the commonest type of lung cancer, which is one of most deadly cancers that possess high morbidity and mortality all over the world. The function of circular RNA NIMA related kinase 6 (circ_NEK6) in NSCLC is still unknown. Therefore, circ_NEK6 is worth studying in detail. METHODS: RT-qPCR and western blot assays were employed to detect gene expression. Colony formation, EdU, JC-1, flow cytometry, and Transwell assays were implemented to explore the function of circ_NEK6 on biological activities of NSCLC cells. Mechanism experiments were conducted to unveil the relationship among molecules. RESULTS: Circ_NEK6 expression was highly expressed in NSCLC tissues and cells. Functionally, the silencing of circ_NEK6 could effectively suppress NSCLC cell proliferation, migration and invasion. Circ_NEK6 sequestered miR-382-5p to fortify the expression of breast carcinoma amplified sequence 2 (BCAS2) in NSCLC. Besides, BCAS2 had tumor-promoting function in NSCLC. Furthermore, the effects of down-regulated circ_NEK6 on the malignant behaviors of NSCLC cells were totally recovered by miR-382-5p inhibition or BCAS2 overexpression. CONCLUSIONS: Circ_NEK6 served as a competing endogenous RNA (ceRNA) of BCAS2 by absorbing miR-382-5p, which may be treated as a novel promising target for the treatment of NSCLC.

The predictive values of serum dickkopf-1 and circulating tumor cells in evaluating the efficacy of transcatheter arterial chemoembolization treatment on hepatocellular carcinoma.

In this study, we aim to explore the values of serum dickkopf-1 (DKK1) and circulating tumor cells (CTCs) in predicting the efficacy and prognosis of transcatheter arterial chemoembolization (TACE) treatment on patients with hepatocellular carcinoma (HCC). We did a retrospective analysis on 155 HCC patients who underwent TACE treatment. The patients were divided into response group (complete response and partial response) and nonresponse group (stable disease and progressive disease), and their changes in serum DKK1 and CTCs after TACE were recorded. Receiver operating characteristic curve and survival analysis were used to assess the predictive values of DKK1 and CTCs for TACE efficacy and long-term prognosis of HCC. We found that the levels of preoperative DKK1 and CTCs in patients with HCC had a moderate positive correlation (r = 0.54). After TACE treatment, the serum DKK1 and CTCs in the response group were significantly decreased compared to pretreatment levels (P < .05), whereas the nonresponse group showed significantly increased serum DKK1 and CTCs levels (P < .05). The largest area under the curve (AUC) was achieved when using >0.02 µg/L reduction in DKK1 level after 4 weeks of TACE to predict the efficacy of TACE treatment (AUC = 0.913, 95% confidence interval: 0.856-0.952, P < .001), with the sensitivity of 78.26% and the specificity of 88.07%. The overall survival, disease-free survival, and 5-year survival rates were all significantly lower in the patients with positive preoperative levels of serum DKK1 and CTCs. COX multivariate regression analysis showed that Eastern Cooperative Oncology Group score, and preoperative levels of serum DKK1 and CTCs are independent influencing factors for the prognosis of patients with HCC. Overall, our results demonstrated that serum DKK1 and CTCs levels were good biomarkers for predicting the efficacy and prognosis of TACE treatment in patients with HCC. Moreover, these parameters exhibited different characteristics, and might have different potential applications.

Long noncoding RNA FOXD2-AS1 incuced gastric cancer cell MGC-803 to apatinib resistance by regulating miR-185-5p/CCND2 modulating axis / 中国肿瘤生物治疗杂志

@# Objective: To investigate the molecular mechanism of lncRNA FOXD2-AS1 participating in apatinib resistance in gastric cancer cells by regulating miR-185-5p/CCND2 axis. Methods: The gastri cancer tissues and corresponding paracancerous tissues of 25 patients with gastric cancer were collected from April 2016 to December 2017 in the Fifth People’s Hospital of Wuxi City. The expressions of FOXD2-AS1, miR-185-5p, and cyclin D2 (CCND2) in gastric cancer tissues or cell lines were examined by quantitative realtime polymerase chain reaction (qRT-PCR). CCK-8 assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay were applied to assess the sensitivity of gastric cancer cells to apatinib. The interaction between FOXD2-AS1, miR-185-5p and CCND2 was explored by dual luciferase reporter gene assay, which was then confirmed by qRT-PCR, and Western blotting. Results: FOXD2-AS1 was highly expressed in gastric cancer tissues and apatinib-resistant gastric cancer cells. Over-expression of FOXD2-AS1 promoted apatinib-resistance of MGC-803/AP cells. Dual luciferase reporter gene assay confirmed that FOXD2-AS1 directly interacted with miR-185-5p and suppressed its expression. miR-185-5p significantly abolished the promotion effect of FOXD2-AS1 on apatinibresistance via inhibiting cell proliferation, invasion and promoting apoptosis of gastric MGC-803/AP cells. miR-185-5p could negatively regulate CCND2 expression; and FOXD2-AS1 promoted the cell proliferation, invasion and inhibited apoptosis of MGC-803/AP cells via down-regulating the inhibition effect of miR-185-5p on CCND2, thus further enhanced the apatinib-resistance of gastric cancer cells. Conclusion: FOXD2-AS1 induced apatinib-resistance of gastric cancer cells by regulating miR-185-5p/CCND2 axis.

Rituximab-conjugated and doxorubicin-loaded microbubbles combined with ultrasound irradiation inhibits proliferation and induces apoptosis in Raji cell lines.

Doxorubicin (DOX) is one of the most important medicines used for the treatment for B cell lymphoma, yet its clinical efficacy is often limited by severe adverse effects. Drug-loaded microbubbles, combined with ultrasound (US) irradiation, has shown great promise in reducing DOX-induced side effects and improving therapeutic efficacy. Nevertheless, these drug-loaded microbubbles are non-targeted microbubbles with comparatively suboptimal efficiency. Therefore, we synthesized targeted and DOX-loaded microbubbles (DMs), combined with US irradiation, for triggering drug release in lymphoma B cells. DMs were coated with rituximab via a biotin-avidin linkage to target Raji cells that overexpress the CD-20 antigen. In the present study, the cell viability after treatment with rituximab-conjugated DMs (RDMs) containing 0.25, 0.5 and 1.0 µg/ml DOX + US was 45.69±6.85, 25.31±2.60 and 15.67±2.83%, respectively, which demonstrated that RDMs + US produced significantly higher cytotoxicity than the other treatments. The early apoptosis ratio in the Raji cells at 48 h after the treatment was 32.4±2.84%, which was notably higher than the ratio in the other treatment groups. The results confirm the hypothesis that US-mediated targeting of CD-20-positive B cell lymphoma and the use of DMs may improve the DOX therapeutic efficiency.

A comparison of TiO2 and ZnO nanoparticles as photosensitizers in photodynamic therapy for cancer.

The TiO2 and ZnO nanoparticles are the most promising next-generation photodynamic therapy (PDT) photosensitizers. This paper reports a one-to-one comparison of TiO2 and ZnO nanoparticles as photosensitizers in photodynamic therapy of cancer. After incubating SMMC-7721 hepatocarcinoma cells with TiO2 and ZnO nanoparticles, we irradiated the cells with ultraviolet (UV) light and formation of intracellular reactive oxygen species (ROS) was monitored using the dichloro-dihydro-fluorescein diacetate (DCFH-DA) method. The cytotoxicities of ZnO and TiO2 nanoparticles as photosensitizers in cancer PDT were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, the mRNA and protein expression levels of apoptosis-related gene, including Bax, Bcl-2, and Caspase 3 were examined using RT-PCR and Western blot to elucidate the possible molecular mechanisms involved. Our results demonstrated that both TiO2 and ZnO nanoparticles could generate ROS within the tumor cells after irradiation, which in turn could attack the cancer cells. The caspase-dependent apoptosis was thus induced, resulting in anticancer activity. When the therapeutic effects were compared, no differences between the TiO2 and ZnO nanoparticles were observed for PDT. Either TiO2 or ZnO nanoparticles can therefore be used in the near future as alternative photosensitizers in targeted tumor PDT when light is directly focused on the lesion.