hsa_circ_0007919 promotes pancreatic cancer metastasis by modulating Sp1-mediated THBS1 transcription.

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second-generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT-PCR and Kaplan-Meier survival curves. Gain- and loss-of-function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC.

CA19­9 is a significant prognostic factor in stage III gastric cancer patients undergoing radical gastrectomy.

BACKGROUND: Due to the great heterogeneity of gastric cancer (GC), the prognosis of patients within a stage is very different. Therefore, it is necessary to identify the high risk factors for postoperative recurrence and metastasis and take appropriate therapeutic strategies to improve the prognosis of patients. In this study, we aimed to explore the prognostic significance of preoperative and postoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19 - 9 (CA19-9) and carbohydrate antigen 72 - 4 (CA72-4) in patients with stage I, II and III GC who underwent radical gastrectomy. METHODS: A total of 580 patients who underwent curative surgical resection and had not received neoadjuvant chemotherapy were included in this study. The relationship between clinicopathological features and recurrence was analysed. Survival analysis was performed by Kaplan-Meier curve. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors in GC patients. RESULTS: Among patients with stage III GC, the recurrence free survival (RFS) and overall survival (OS) of patients with CA19-9>35 U/mL were significantly lower than those with CA19-9 ≤ 35 U/mL; CA19-9 was always a significant independent marker. CEA and CA72-4 were sometime useful to predict RFS or OS alternatively in the pre- or postoperative period. The only other independent significant factors for prognosis in our study were lymph node metastases for RFS and postoperative adjuvant chemotherapy for OS. CONCLUSION: Preoperative and postoperative CA19-9 values are independent risk factors for predicting prognosis in stage III GC after curative gastrectomy.

Factors impacting human exposure to legacy and emerging contaminants in residential dust in Beijing, China: Characteristics of indoor microenvironment.

Exposure to indoor dust is of concern since dust may be contaminated by various toxic chemicals and people spend considerable time indoors. Factors impacting human exposure risks to contaminants in indoor dust may differ from those affecting the loadings of contaminants, but the dominant factors have not yet been well clarified. In this study, the occurrence, human exposure, and related influencing factors of several classes of legacy and emerging contaminants in residential dust across Beijing were investigated, including per- and polyfluoroalkyl substances (PFASs) and three types of flame retardants (FRs), i.e., organophosphate esters (OPEs), polybrominated diphenyl ethers (PBDEs), and novel halogenated FRs (NHFRs). OPEs (median: 3847 ng/g) were the most abundant group, followed by PBDEs (1046 ng/g) and NHFRs (520 ng/g). PFASs (14.3 ng/g) were one to two orders of magnitude lower than FRs. The estimated daily intakes of these contaminants were relatively higher for toddlers than other age groups, with oral ingestion being the main exposure pathway compared with dermal contact. Higher human exposure risks were found in new buildings or newly finished homes due to the elevated intake of emerging contaminants (such as OPEs). Furthermore, higher risks were also found in homes with wooden floors, which were mainly associated with higher levels of PFASs, chloroalkyl and alkyl OPEs, compared with tile floors. Citizens in the urban area also showed higher exposure risks than those in the suburban area. The quantity of household appliances and finishing styles (simple or luxurious) showed an insignificant impact on overall human exposure risks despite their significant effect on the levels of some of the dust contaminants. Results in this study are of importance in understanding human exposure to the co-existence of multiple contaminants in indoor dust.