PurposeThis study aimed to probe into the associations among circular RNA ZFR (circ-ZFR), miR-130a/miR-107, and PTEN, and to investigate the regulatory mechanism of circ-ZFR‒miR-130a/miR-107‒PTEN axis in gastric cancer (GC).Materials and MethodsGSE89143 microarray data used in the study were acquired from publicly available Gene Expression Omnibus database to identify differentially expressed circular RNAs inGC tissues. The expressions of circ-ZFR, miR-130a, miR-107, and PTEN were examined by real-time reverse transcription polymerase chain reaction, while PTEN protein expression was measured by western blot. The variation of GC cell proliferation and apoptosis was confirmed by cell counting kit-8 assay and flow cytometry analysis. The targeted relationships among circZFR, miR-130a/miR-107, and PTEN were predicted via bioinformatics analysis and demonstrated by dual-luciferase reporter assay and RNA immunoprecipitation assay. The impact of ZFR on gastric tumor was further verified in xenograft mice model experiment.ResultsCirc-ZFR and PTEN were low-expressed whereas miR-107 and miR-130a were highexpressed in GC tissues and cells. There existed targeted relationships and interactions between miR-130a/miR-107 and ZFR/PTEN. Circ-ZFR inhibited GC cell propagation, cell cycle and promoted apoptosis by sponging miR-107/miR-130a, while miR-107/miR-130a promoted GC cell propagation and impeded apoptosis through targeting PTEN. Circ-ZFR inhibited cell proliferation and facilitated apoptosis in GC by sponging miR-130a/miR-107 and modulating PTEN. Circ-ZFR curbed GC tumor growth and affected p53 protein expression in vivo.ConclusionCirc-ZFR restrained GC cell proliferation, induced cell cycle arrest and promoted apoptosis by sponging miR-130a/miR-107 and regulating PTEN.

Alanine serine cysteine-preferring transporter 2 (ASCT2; also known as SLC1A5) is an important glutamine transporter, and it serves a crucial role in tumor growth and progression. ASCT2 is highly expressed in numerous types of cancer, but the pathological significance of its expression in epithelial ovarian cancer (EOC) remains unclear. The mechanistic target of rapamycin (mTOR) level is hyperelevated in a number of tumor types, including ovarian cancer. The aim of the present study was to elucidate the prognostic role of ASCT2 and phosphorylated (p)-mTOR in EOC. The levels of ASCT2 and p-mTOR/mTOR were detected in normal ovarian tissues, benign ovarian tumors, borderline ovarian tumors and EOC tissues by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The protein levels of ASCT2 and p-mTOR in EOC patients were then detected by immunohistochemistry (IHC). Furthermore, EOC tumor sections were stained for Ki-67 and cluster of differentiation 34 (CD34) to assess proliferation and microvessel density by IHC. The results of RT-qPCR and western blot analysis demonstrated that ASCT2 and p-mTOR protein levels were significantly higher in EOC tissues compared with those in other groups. IHC analysis of 104 EOC tissues suggested that ASCT2 expression was associated with clinicopathological parameters, including International Federation of Gynecology and Obstetrics stage, pathological grade, serum cancer antigen 125 level, Ki-67 status and CD34 status. Kaplan-Meier survival curve analysis indicated that high expression of ASCT2 and p-mTOR were important factors predicting a poor prognosis for patients with EOC. The expression levels of ASCT2 and p-mTOR in EOC were positively correlated (r=0.385, P<0.001). This positive correlation between ASCT2 and p-mTOR indicates that they have a synergistic effect on the growth and development of early EOC. The combined detection of ASCT2 and p-mTOR may serve as a potential marker to inform diagnosis, postoperative follow-up requirements and targeted therapy options for patients with early-stage EOC, but not for terminal-stage patients.

Vascular endothelial growth factor C (VEGF‐C) has been reported to be responsible for the lymphatic vessel density, tumor staging and lymph node metastasis, resulting in the failure of nasopharyngeal carcinoma (NPC) after radiotherapy. Therefore, the aim of this study was to explore the effects and the underlying mechanism of VEGF‐C on the radiotherapy and in the human NPC cell lines CNE‐2. In our study, VEGF‐C silenced CNE‐2 cells were stably established. Different small interfering VEGF‐C (si‐VEGFC) were transfected into CNE‐2 cells and combined with 8 Gy X‐ray. The proliferation, cloning ability, DNA damage, and apoptosis of CNE‐2 cells were evaluated by counting kit‐8 (CCK‐8), colony‐forming assay, comet assays, and flow cytometry, respectively. Moreover, the VEGFC knockdown involved signaling pathways in CNE‐2 cells were predicted by polymerase chain reaction (PCR) array, and validated by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and Western blot analysis. Results demonstrated that silencing VEGF‐C combined with radiation can significantly inhibit the proliferation and cloning ability, while increase the apoptosis and DNA damage of CNE‐2 cells, thereby promote the radiosensitivity. Furthermore, the effects of silencing VEGF‐C probably through activating the NF‐kB signal pathway. In conclusion, the study demonstrated that VEGF‐C may be a potential target to increase the radiosensitivity in NPC by activating NF‐kB signaling.

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