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Circular RNA 0067934 (circ_0067934) has been revealed as a cancer driver in multiple human malignancies, whereas its action in the pathogenesis of ovarian cancer (OC) remains unclear. This study focuses on the function of circ_0067934 in tumorigenesis and cisplatin (DDP) resistance in OC and the molecular mechanism.Expression of circ_0067934 in OC tissues and cells was examined, and its correlation with the clinical characteristics of patients was analyzed. Candidate targets of circ_0067934 were predicted using bioinformatics systems. Binding relationships between circ_0067934 and microRNA (miR)-545-3p and between miR-545-3p and inorganic pyrophosphatase 1 (PPA1) were validatedCirc_0067934 was overexpressed in OC samples and associated with advanced tumor staging and lymph node metastasis. Downregulation of circ_0067934 reduced DDP resistance of the DDP-resistant A2780/DDP cell line and reduced cell proliferation and invasion, but the malignant behaviors of OC cells were restored after further miR-545-3p downregulation. Circ_0067934 served as a sponge for miR-545-3p and diminished its suppressive effect on PPA1 translation. Artificial upregulation of PPA1 enhanced proliferation, invasion and DDP resistance of A2780/DDP cells, and it reduced phosphorylation of the pro-apoptotic JNK signaling. Similar results were foundThis study suggests that circ_0067934 sequesters miR-545-3p and enhances PPA1 expression to promote tumorigenesis and DDP resistance in OC. This study may provide novel approaches in the management of OC.

As a prevalent tumor among women, breast cancer is still an incurable disease due to drug resistance. In this study, we report microRNA‐221 to have a significant effect on breast cancer resistance to adriamycin. The microRNA‐221 is elevated in tumor tissue compared with nearby nontumor samples, as well as in breast cancer cell line with adriamycin resistance (MCF‐7/ADR) compared to its parental line (MCF‐7) and the normal breast epithelial cell line (MCF‐10A). Enforced level of microRNA‐221 promotes cancer resistance to adriamycin, which in turn sustains cell survival and exacerbates malignant formation. Reciprocally, the silence of microRNA‐221 in cancer cells augments the sensitivity to chemotherapy, thereby resulting in enhanced apoptosis of MCF‐7/ADR cells. Mechanistically, we identify PTEN as a direct target of microRNA‐221, which was conversely associated with a microRNA‐221 level in breast tumors. The knock‐down of PTEN partially reversed the stimulatory role of microRNA‐221 in the modulation of the Akt/mTOR signaling. Taken together, these findings suggest microRNA‐221 suppresses PTEN transcription and activates Akt/mTOR pathway, which in turn enhances breast cancer resistance to adriamycin and promotes cancer development. Our data thus illuminate the microRNA‐221/PTEN axis may act as a promising strategy for the treatment of chemotherapy‐resistant breast tumors., The miR‐221 suppresses PTEN transcription and activates Akt/mTOR pathway, which in turn enhances breast cancer resistance to adriamycin and promotes cancer development.

Stress is associated with an increased risk of lung metastasis in melanoma. However, the underlying mechanism is elusive. Oxytocin (OXT), a neurohormone produced by the hypothalamus, plays a vital role in laboring induction and lactation. Emerging evidence suggests that OXT also regulates human emotions, social cognition, social behaviors and stress-related disorders. Here, we reported that a significant up-regulation of oxytocin receptors (OXTRs) was observed in malignant melanoma. The activation of OXTRs dramatically promoted migration, invasion and angiogenesis but not the proliferation of melanoma cells in vitro and in vivo via β-arrestin 2-dependent ERK-VEGF/MMP-2 pathway. Next, chronic restraint stress significantly elevated the plasma level of OXT. Notably, 21 days chronic restraint stress facilitated lung metastasis of melanoma and reduced overall survival in mice, which were largely abrogated by knocking down either OXTR or β-arrestin 2. These findings provide evidence that chronic stress hormone-OXT promotes lung metastasis of melanoma via a β-arrestin 2-dependent mechanism and suggest that OXT, a novel pro-metastasis factor, is a potential therapeutic target for melanoma.

TIPE2 participates in multiple types of cancer development. However, its mechanism underlying chemoresistance in osteosarcoma has not been elucidated. Herein, we observed the expression of TIPE2 and MDR1 in cis-platin-resistant osteosarcoma tissues and cell lines. Compared to their matched sensitive cell lines and tissues, TIPE2 was downregulated while MDR1 expression was increased. Further investigation showed that overexpression of TIPE2 effectively inhibited MDR1 expression and greatly sensitized osteosarcoma cells to cis-platin, both in vivo and in vitro. Mechanistically, TIPE2 inhibited the transcription of the MDR1 promoter by interfering with the TAK1-NF-κB and -AP-1 pathways. Overall, our results elucidated for the first time that TIPE2 sensitizes osteosarcoma cells to cis-platin through downregulation of MDR1 and may be a novel target in osteosarcoma therapy.