Recent studies indicate that circular RNA (circRNA) is involved in tumorigenesis, but its role in triple-negative breast cancer (TNBC) remains largely unknown. In this study, we characterized the role of circ-ITCH in TNBC and found that circ-ITCH was significantly down-regulated in TNBC tissues and cell lines and closely associated with poor prognosis. We therefore constructed the MDA-MB-231 and BT-549 TNBC cell lines stably expressing circ-ITCH by lentiviral vectors to determine its underlying mechanisms in TNBC progression. Most importantly, over-expression of circ-ITCH remarkably inhibited TNBC proliferation, invasion and metastasis both in vitro and in vivo. Mechanistically, we found that circ-ITCH acts as a sponge for miR-214 and miR-17 to increase expression of its ITCH linear isoform, thereby inactivating Wnt/βcatenin signaling. Our combined results show for the first time that circ-ITCH is a tumor suppressor, a promising prognostic biomarker in TNBC and that its restoration could well be a successful strategy in TNBC.

BackgroundAccumulating evidence suggests that circular RNAs (circRNAs) play critical roles in carcinomas. However, the contributions of circRNAs to breast cancer remain unclear. Herein, we determined the role of circZNF609 in breast cancer.MethodsA total of 143 breast cancer and 38 normal tissues were collected to assess the expression of circZNF609 and its relationship with breast cancer prognosis. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circZNF609 in breast cancer progression and its underlying molecular mechanisms.ResultsCircZNF609 was markedly over-expressed in breast cancer tissues and cell lines, and high circZNF609 expression was closely associated with poor outcome. Silencing of circZNF609 inhibited the malignant phenotype of breast cancer in vitro and in vivo. Mechanistically, circ-ZNF609 served as a sponge of miR-145-5p to elevate p70S6K1 expression. Moreover, miR-145-5p overexpression or p70S6K1 knockdown abrogated the oncogenic effects of circZNF609 in breast cancer. In addition, clinically, a strong negative correlation was observed between the expression of circZNF609 and miR-145-5p in breast cancer tissues (r=–0.597, P<0.001), whereas a positive correlation between circZNF609 and p70S6K1 expression (r=0.319, P<0.001).ConclusionThese data suggest that circZNF609 contributes to breast cancer progression, at least partly, by modulating the miR-145-5p/p70S6K1 axis, and it may be a potential therapeutic target for breast cancer.

No abstract

Yuan-zhi-san (YZS) is a classic type of Traditional Chinese Medicine, which has been reported to aid in the treatment of Alzheimer's disease (AD). The present study aimed to investigate the effects of YZS on tau protein aggregation, a hallmark of AD pathology, and its possible mechanisms. The results demonstrated that YZS improved learning and memory abilities, and decreased the severity of AD pathology in β-amyloid (Aβ 1-40)-induced AD rats. Moreover, YZS administration inhibited the hyperphosphorylation of tau protein at Ser199 and Thr231 sites. Several vital enzymes in the ubiquitin-proteasome system (UPS), including ubiquitin-activating enzyme E1a/b, ubiquitin-conjugating enzyme E2a, carboxyl terminus of Hsc70-interacting protein, ubiquitin C-236 terminal hydrolase L1 and 26S proteasome, were all significantly downregulated in AD rats, which indicated an impaired enzymatic cascade in the UPS. In addition, it was identified that YZS treatment partly increased the expression levels of these enzymes in the brains of AD rats. In conclusion, the present results suggested that YZS could effectively suppress the hyperphosphorylation of tau proteins, which may be partially associated with its beneficial role in restoring functionality of the UPS.

ObjectivesThe aim of this study was to compare the metastatic patterns of synchronous bone metastasis (SBM) and metachronous bone metastasis (MBM) in nasopharyngeal carcinoma (NPC).MethodsThis study included bone metastases in NPC patients from 2005 to 2016 in a Chinese hospital. Cohort 1 was collected from 2005 to 2010 for discovery, and Cohort 2 from 2011 to 2016 for validation. The chi‐squared test, Wilcoxon rank sum test, and Kaplan–Meier technique were used to compare site, time, and survival between cohorts 1 and 2. Prognostic factors were analyzed using univariate or multivariate Cox regression.ResultsCohort 1 had 112 individuals with SBM and 394 with MBM, and cohort 2 had 328 with SBM and 307 with MBM. The thoracic vertebra was the most frequently affected site of metastasis. Patients with SBM more often had metastasis to the cervical vertebrae compared with patients with MBM (34.5% vs. 22.3%, p < 0.05). Patients with SBM had better overall survival (42.2 months, 95% CI: 33.9–50.7) than patients with MBM (24.9 months, 95% CI: 22.2–28.7). Age at bone metastasis detection, metastasis to other organs, and more bone metastasis locations were associated with worse prognosis. The majority of MBMs occurred at 7 to 18 months after NPC diagnosis.ConclusionRadiotherapy does not modify the metastatic patterns of NPC bone metastases. Patients with SBM tend to have metastasis to the cervical vertebra, which is close to the nasopharynx. Paying more attention to bone metastases during follow‐up in the first 2 years after an NPC diagnosis.