Long non-coding RNAs (lncRNAs) are non-coding RNAs that are >200 nucleotides in length. Recent studies have identified a number of lncRNAs with critical roles in various biological processes including tumorigenesis. Zinc finger antisense 1 (ZFAS1) is a lncRNA that has recently been reported to be involved in the progression of several human cancers. However, the biological function of ZFAS1 in breast cancer remains to be elucidated. In order to determine the effect of ZFAS1 in breast cancer cells, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to measure ZFAS1 expression in cells from breast cancer cell lines. In addition, gain-of-function experiments were performed in vitro to investigate the biological role of ZFAS1. The results revealed that ZFAS1 expression was significantly downregulated in breast cancer cell lines when compared with the levels in controls. In vitro experiments also demonstrated that ZFAS1 overexpression significantly suppressed cell proliferation by causing cell cycle arrest and inducing apoptosis in breast cancer cells. Further functional assays indicated that ZFAS1 overexpression inhibited cell migration and invasion by regulating epithelial-mesenchymal transition. These findings indicated that the lncRNA ZFAS1 may be a tumor suppressor in breast cancer, and thus, may serve as a potential therapeutic target for patients with breast cancer.
Berberine is one of the main active constituents of Rhizoma coptidis, a traditional Chinese medicine, and has long been used for the treatment of gastrointestinal disorders. The present study was designed to investigate the effects of berberine on the intestinal mucosal barrier damage in a rat uremia model induced by the 5/6 kidney resection. Beginning at postoperative week 4, the uremia rats were treated with daily 150 mg/kg berberine by oral gavage for 6 weeks. To assess the intestinal mucosal barrier changes, blood samples were collected for measuring the serum D-lactate level, and terminal ileum tissue samples were used for analyses of intestinal permeability, myeloperoxidase activity, histopathology, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity. Berberine treatment resulted in significant decreases in the serum D-lactate level, intestinal permeability, intestinal myeloperoxidase activity, and intestinal mucosal and submucosal edema and inflammation, and the Chiu's scores assessed for intestinal mucosal injury. The intestinal MDA level was reduced and the intestinal SOD activity was increased following berberine treatment. In conclusion, berberine reduces intestinal mucosal barrier damage induced by uremia, which is most likely due to its anti-oxidative activity. It may be developed as a potential treatment for preserving intestinal mucosal barrier function in patients with uremia.
The objectives of the present study were to obtain the multigene mutation spectra of female breast cancer patients in Northeast China, to explore the correlation between mutations and clinicopathological characteristics, and to identify genetic mutations that correlate with the prognosis and survival of breast cancer patients. An Ion Torrent sequencing platform was used to detect mutations, including 31 known gene mutations associated with breast cancer, in 621 specimens from 286 breast cancer patients. A total of 286 patients were enrolled in this study. Eleven harmful/pathogenic gene mutations were found in 54.2% (155/286) of the patients, and 179 somatic nonsynonymous mutations were detected. Approximately 5.6% (16/286) of the patients carried two or more gene mutations. Among the 11 pathogenic gene mutations, those in PIK3CA were the most common and were detected in 65.4% (117/179) of the patients; TP53 gene mutations were the second most common and were detected in 20.7% (37/179) of the patients. Additional mutations were found in AKT (14/179; 7.8%) and PTEN (4/179; 2.2%), and mutations in the remaining 7 genes were each detected in approximately 0.6% (1/179) of the patients. Excluding 6 cases of breast ductal carcinoma in situ, the remaining 280 breast cancer cases were divided into four groups by molecular subtype, and the mutation frequencies of the 11 breast cancer-associated genes differed among the four groups. Furthermore, these 280 breast cancer cases were divided into two clinically relevant therapeutic groups: The HR + /HER2and triple-negative groups. The triple-negative group had a high frequency of TP53 mutations (21.8%) and a low frequency of PIK3CA mutations (21.8%), whereas the HR + /HER2group harbored TP53 mutations at a low frequency (10.1%) and PIK3CA mutations at a high frequency (50.0%). Cancerous, paracancerous, and normal tissues were collected from 72 patients and subjected to next-generation sequencing. The types and frequencies of somatic nonsynonymous mutations differed among the three studied tissue types, reflecting the genetic heterogeneity of different tissues from the same individual. In addition, tissues from 70 patients (excluding 2 patients with ductal carcinoma in situ) were divided into four groups according to molecular subtype, and the gene mutation frequencies in cancerous, paracancerous, and normal tissues differed among the four groups. After normalization, gene mutations were detected at a higher rate in cancerous tissues than in paracancerous and normal tissues in all groups, except for the HER2-positive group (which had a small sample size). In addition, Cox multivariate analyses of clinicopathological data, gene sequencing results, and 5-year survival rates of the 286 patients showed that gene mutations in the PTEN-PI3K/AKT signaling pathway were independently associated with a poor prognosis (P<0.05). In conclusion, mutations in the PTEN-PI3K/AKT signaling pathway may be valuable in the prediction of the prognosis and survival of breast cancer patients.
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