Circular RNA_0000326 accelerates breast cancer development via modulation of the miR-9-3p/YAP1 axis.

Circular RNA (circ)_0000326 has been reported in bladder cancer and cervical cancer and is concerned to be involved with the development of cancerous cells. Whereas, there have been no reports concentrating on the influences of circ_0000326 in breast cancer (BC). Therefore, the latent modulatory mechanisms of circ_0000326 in BC are researched. circ_0000326 expression in BC tissues and correlative cells was evaluated via RT-qPCR, and the relevance between circ_0000326 expression and overall survival and the clinicopathological feature was also investigated. After a series of transfection, the effects of circ_0000326, microRNA-9-3p (miR-9-3p), and Yes-associated protein 1 (YAP1) in BC cell growth, invasion, and stemness were studied by CCK-8, flow cytometry, Transwell, and sphere-forming assays. The binding sites and correlation of circ_0000326, miR-9-3p, and YAP1 were certified via starBase website, luciferase reporter assay, and Pearson's χ2 test. The in vivo experiment was evaluated by establishing a subcutaneous tumorigenesis model. High-expressed circ_0000326 in BC tissues and cells was discovered, which was connected with an undesirable prognosis. Silencing of circ_0000326 visibly inhibited MCF-7 and BT549 cell growth, invasion, stemness, meanwhile declining the protein levels of SRY-related high-mobility group box gene 2 (SOX2) and octamer binding transcription factor 4 (OCT4). miR-9-3p was a sponger of circ_0000326, which was negatively regulated by circ_0000326. Moreover, YAP1 was confirmed as a target gene of miR-9-3p. circ_0000326 affected BC cell behaviors via mediating miR-9-3p and YAP1. Furthermore, circ_0000326 silencing prohibited tumor growth of BC in vivo. The research uncovered that circ_0000326 facilitated BC development via mediating the miR-9-3p/YAP1 axis.

RNF43 Inhibits Cancer Cell Proliferation and Could be a Potential Prognostic Factor for Human Gastric Carcinoma.

BACKGROUND/AIMS: RNF43 is a member of transmembrane E3 ubiquitin ligases and plays important roles in tumor formation progression. In current study, we aimed to explore RNF43 expression and analyze its role in gastric carcinoma. METHODS AND RESULTS: The level of RNF43 was detected in 77 cases of gastric carcinoma and matched normal tissues by real-time PCR, western blotting and immunohistochemistry. We found that the expression of RNF43 was significantly down-regulated in the gastric carcinoma tissues compared to the normal mucosae (all P<0.001). In addition, RNF43 was significantly correlated with histological differentiation (P = 0.001), T-stage cancer (P<0.001), depth of invasion (P<0.001), metastasis of regional lymph nodes (P<0.001), pTNM stage (P<0.001) and survival (P = 0.021). We further explored the biological functions of RNF43 in gastric carcinoma cell lines. Both gain- and loss-function assays show that RNF43 could suppress cell proliferation while promotes cell apoptosis. Further, we found that RNF43 was positively correlated with p53 and cleaved-caspase3 and negatively correlated with Ki67 and Lgr5. CONCOLUSION: In conclusion, RNF43 might act as a tumor suppressor in gastric carcinoma and might be a potential indicator for the clinical assessment of gastric cancer prognosis.

Accuracy of 16/18G core needle biopsy for ultrasound-visible breast lesions.

BACKGROUND: To assess the accuracy of ultrasound-guided 16G or 18G core needle biopsy (CNB) for ultrasound-visible breast lesions, and to analyze the effects of lesion features. METHODS: Between July 2005 and July 2012, 4,453 ultrasound-detected breast lesions underwent ultrasound-guided CNB and were retrospectively reviewed. Surgical excision was performed for 955 lesions (566 with 16G CNB and 389 with 18G CNB) which constitute the basis of the study. Histological findings were compared between the ultrasound-guided CNB and the surgical excision to determine sensitivity, false-negative rate, agreement rate, and underestimation rate, according to different lesion features. RESULTS: Final pathological results were malignant in 84.1% (invasive carcinoma, ductal carcinoma in situ, lymphoma, and metastases), high-risk in 8.4% (atypical lesions, papillary lesions, and phyllodes tumors), and benign in 7.5%. False-negative rates were 1.4% for 16G and 18G CNB. Agreement rates between histological findings of CNB and surgery were 92.4% for 16G and 92.8% for 18G CNB. Overall underestimate rates (high-risk CNB becoming malignant on surgery and ductal carcinoma in situ becoming invasive carcinoma) were 47.4% for 16G and 48.9% for 18G CNB. Agreements were better for mass lesions (16G: 92.7%; 18G: 93.7%) than for non-mass lesions (16G, 85.7%; 18G, 78.3%) (P <0.01). For mass lesions with a diameter ≤10 mm, the agreement rates (16G, 83.3%; 18G, 86.7%) were lower (P <0.01). CONCLUSIONS: Ultrasound-guided 16G and 18G CNB are accurate for evaluating ultrasound-visible breast mass lesions with a diameter >10 mm.

LKB1 inhibits the proliferation of gastric cancer cells by suppressing the nuclear translocation of Yap and ß-catenin.

Liver kinase B1 (LKB1) is known to suppress the proliferation, energy metabolism and mesenchymal transition of various cancer cells, and is involved in the regulation of Hippo-Yes-associated protein (Yap) and the Wnt/ß-catenin signaling pathways. However, the role of LKB1 in gastric cancer (GC) was not fully understood. Thus, in the present study, we studied LKB1 and found that protein expression (0.37±0.061 vs. 0.59±0.108, P=0.006) and the protein ratio of p-Yap/Yap (0.179±0.085 vs. 0.8±0.126, P=0.001) were reduced in 54 gastric adenocarcinoma (GAC) tissues compared with the matched adjacent non-cancerous tissues, using western blotting and RT-qPCR assays. LKB1 expression was also observed decreased in 109 GAC tissues compared with 54 adjacent non-cancerous tissues (χ2=4.678, P=0.0306), and negatively correlated with the nuclear expression of Yap (r=-0.6997) and ß-catenin (r=-0.3510), using immunohistochemical analysis. In GC patients, LKB1 expression was negatively associated with tumor size, tumor infiltration, lymph node metastasis and the TNM stage. LKB1 expression was determined to be positively correlated with longer overall survival of GC patients using Kaplan-Meier analysis (P=0.001). Subsequently, LKB1 expression in human GAC AGS cells was enhanced with a full­length LKB1 transfection. In vitro and in vivo proliferation was inhibited in LKB1-overexpressing GC cells compared with the control cells. Yap and ß-catenin expression were assessed by western blotting and RT-qPCR, and were found to be increased in the cytoplasm but decreased in the nucleus in LKB1-overexpressing GC cells compared with the control cells. The increase in cytoplasmic ß-catenin was reversed by the silencing of LKB1 or Yap with shRNAs in LKB1-overexpressing GC cells. Moreover, Yap and ß-catenin mRNA were barely altered by LKB1 overexpression. Thus, we concluded that LKB1 expression was reduced in GAC tissues but that it correlated positively with better prognosis for GC patients. LKB1 inhibits the proliferation of GC cells by suppressing the nuclear translocation of Yap and ß-catenin.