MicroRNAs (miRNAs) are 22- to 25-nucleotide non-coding RNA molecules that function as negative regulators of gene expression. In previous years, increasing evidence has arisen implicating the involvement of miRNAs in carcinogenesis. In previous studies, the role of miRNA-101 (miR-101) in tumors has been identified as a tumor suppressor and, until now, the role of miR-101 and Rac1 in thyroid cancer has remained undefined. This study revealed that miR-101 is significantly downregulated in papillary thyroid carcinoma (PTC) tissue and thyroid cancer cell lines, and that the downregulated miR-101 is associated with lymph node metastasis. Infection with the miR-101 murine stem cell virus may markedly inhibit cell migration and invasion in TPC-1 and HTH83 thyroid cancer cell lines. Rac1 was demonstrated to be negatively regulated by miR-101 at the post-transcriptional level, via a specific target site within the 3′ untranslated region by dual-luciferase reporter assay. The expression of Rac1 was also observed to inversely correlate with miR-101 expression in PTC tissues; knockdown of Rac1 by shRNA inhibited thyroid cancer cell migration and invasion, resembling that of miR-101 overexpression. Thus, these findings suggested that miR-101 acts as a novel suppressor by targeting the Rac1 gene and inhibiting thyroid cancer cell migration and invasion.
Abstract-Atorvastatin (ATV), an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, is widely prescribed as a lipid-lowering drug. It also inhibits the RhoA-Rho-associated kinase pathway in vascular smooth muscle (SM) cells and critically inhibits SM function. Myocardin is a coactivator of serum response factor, which upregulates SM contractile proteins. The RhoA-Rho-associated kinase pathway, which directly triggers SM contraction, also increases myocardin gene expression. Therefore, we investigated whether ATV inhibits myocardin gene expression in SM cells. In mice injected with ATV (IP 20 g/g per day) for 5 days, myocardin gene expression was significantly downregulated in aortic and carotid arterial tissues with decreased expression of myocardin target genes SM ␣-actin and SM22. Correspondingly, the contractility of aortic rings in mice treated with ATV or the Rho-associated kinase inhibitor Y-27632 was reduced in response to treatment with either KCl or phenylephrine. In cultured mouse and human aortic SM cells, KCl treatment stimulated the expression of myocardin, SM ␣-actin, and SM22. These stimulatory effects were prevented by ATV treatment. ATV-induced inhibition of myocardin expression was prevented by pretreatment with either mevalonate or geranylgeranylpyrophosphate but not farnesylpyrophosphate. Treatment with Y-27632 mimicked ATV effects on the gene expression of myocardin, SM ␣-actin, and SM22, further suggesting a role for the RhoA-Rho-associated kinase pathway in ATV effects. Furthermore, ATV treatment inhibited RhoA membrane translocation and activation; these effects were prevented by pretreatment with mevalonate. We conclude that ATV inhibits myocardin gene expression in vivo and in vitro, suggesting a novel mechanism for ATV inhibition of vascular contraction. Statins inhibit production of isoprenoid intermediates in the cholesterol biosynthetic pathway, such as farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP), to reduce posttranslational modifications of several intracellular signaling proteins, including nuclear lamins, Ras, Rho, Rac, and Rap. 1-3 The Ras and Rho GTPase family members are the major substrates for posttranslational modification by prenylation. 4 These small GTP-binding proteins cycle between the inactive GDP-bound state and active GTP-bound state and play critical roles in the regulation of the actin cytoskeleton and intracellular signaling pathways. It has been shown that statins regulate subcellular location 1 and activation of Ras and Rho. 5 The inhibitory effect of statins on prenylation of these small G proteins, for example, RhoA, and, therefore, the RhoA-Rho-associated kinase (ROCK) pathway, is known to contribute to protection of the cardiovascular system beyond their cholesterol-lowering effects. 6 It is well known that the ROCK pathway stimulates contraction through inhibition of myosin light-chain phosphatase or phosphorylation of myosin light chain 20. 7,8 Statins attenuate spontaneous smooth muscle (SM) tone through inhibition of the...
The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of biological processes and is related to the tumorigenesis and progression of multiple tumors. However, the clinical application of SOX17 for breast cancer prognosis is currently limited. The aim of this study was to investigate the clinicopathologic and prognostic significance of SOX17 expression in human breast cancer. qPCR and western blot assays were performed to measure the expression of SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and corresponding noncancerous tissues. A SOX17 overexpression cell model was used to examine changes in cell growth in vitro. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of SOX17 expression in 187 additional breast cancer patients. Our results showed that SOX17 expression was decreased at both the messenger RNA (mRNA) and protein levels in the breast cancer cell lines and tissues, and that SOX17 overexpression could strongly suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression was strongly correlated with higher tumor grade (P = 0.002), lymph node metastasis (P < 0.001), and tumor node metastasis (TNM) stage (P = 0.001) and had poorer disease-free survival (DFS) and overall survival (OS) compared to normal SOX17 expression (P = 0.002 and 0.001, respectively). Univariate and multivariate analyses indicated that lower SOX17 expression was an independent prognostic factor for DFS (P = 0.007; HR = 2.854; 95 % CI 1.326-6.147) and OS (P = 0.005; HR = 5.035; 95 % CI 1.648-15.385) for breast cancer. Our findings indicate that SOX17 expression is a useful prognostic biomarker for breast cancer.
A rapid, sensitive, precise and accurate quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the measurement of tertiary butylhydroquinone (TBHQ) in commercial edible oil was developed and validated. After extraction, samples without prior concentration were analyzed by ion trap MS/MS in MS and MS/MS negative ion detection modes using electrospray ionization. The method showed satisfactory recovery (81.9 ± 1.9–109.6 ± 4.6%), sensitivity (lower limit of quantitation of 48 µg/L for TBHQ) and precision (≤5.2%), as well as excellent linearity (R2 ≥ 0.99), with a run time of only 5 min. The method was successfully applied to the determination of TBHQ in commercial samples of edible oils containing various natural antioxidants, providing a promising and convenient entry to monitor the use of TBHQ. PRACTICAL APPLICATIONS HPLC coupled with the ion trap tandem mass spectrometry method with high selectivity, sensitivity, precision and accuracy is suitable for routine quality control analysis of tertiary butylhydroquinone (TBHQ) in edible oils. Analyzing each oil sample by this method takes only 5 min. Moreover, the evaluation of TBHQ in commercial edible oil by this method does not suffer from interference of some coexisting potential peculiar chemical components.
Brick tea-type fluorosis (BTF) due to a high intake of brick tea is possible in Tibetan populations, and dental fluorosis (DF) and skeletal fluorosis (SF) are its primary manifestations. To determine the prevalence of DF and SF and their relationships with brick tea intake in Tibetan populations, a literature review was conducted for studies published between 1994 and 2021. The available evidence revealed that brick tea may be produced from older stems and leaves of the tea plant and that the fluoride content of brick tea exceeds the national standard. The harsh environment of the plateau has led to limited food sources for the local Tibetan people who form the habit of drinking tea leaves as a satiation solution to digest greasy food and replenish vitamins, and regular consumption of brick tea leads to excessive exposure of Tibetan residents to fluoride. Studies in Tibet showed that the prevalence of DF in children was 14.06–75.93% in different districts, and the overall pooled prevalence of DF was 26.08%. The prevalence of SF in adults was 19.90–74.77% in different Tibetan districts, and the overall pooled prevalence of SF was 33.84%. The analysis of risk factors showed that the prevalence of BTF may be related to high-altitude and different working and living conditions, and BTF in children may be associated with fluoride intake during mothers’ pregnancy and lactation. With the development of bioinformatics research, gene polymorphisms were suspected to be related to susceptibility to fluorosis in Tibetan populations. The study of BTF in Tibetan people needs to be further investigated and standardized, and additional studies evaluating the pathogenesis and preventive measures of BTF are warranted.
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