Manningcruz6508

The present results expanded the mutational spectrum of the BSCL2 gene in the Chinese population and suggested that introns 2 and 3 of BSCL2 are prone to recombination. Thus, exon 3 deletion should be considered for patients with CGL2 when only one BSCL2 variant is detected through WES.The Nemo‑like kinase (NLK), a conserved serine/threonine kinase, plays a critical role in the regulation of a variety of transcription factors, with important roles in determining cell fate. Although recent studies have demonstrated decreased expression patterns of NLK in various types of human cancer, the functional mechanism of NLK in cancer development has not been elucidated. Here, in the present study overexpression of NLK was found to inhibit the growth and migration of the non‑small cell lung cancer A549 cell line. NLK was subsequently found to interact with 14‑3‑3ζ (also known as YWHAZ), which is responsible for E‑cadherin silencing during epithelial‑mesenchymal transition (EMT). Furthermore, NLK overexpression was able to restore the expression of E‑cadherin inhibited by 14‑3‑3ζ. Notably, NLK interacts with 14‑3‑3ζ and prevents its dimerization, which is essential for 14‑3‑3ζ stability and function. By fusing two copies of the 14‑3‑3ζ gene, via a Gly‑rich linker, a non‑dissociable dimer of 14‑3‑3ζ was formed. It was found that NLK was unable to restore the expression of E‑cadherin inhibited by the overexpression of the fused dimer of 14‑3‑3ζ. In addition, the increased ability of migration induced by the overexpression of fused 14‑3‑3ζ dimer could not be altered by NLK overexpression. The results from the present study indicate that NLK is a negative regulator of 14‑3‑3ζ and plays a tumor suppressive role in the inhibition of cancer cell migration.MicroRNA (miRNA/miR)‑21‑5p has been proposed as an oncogenic miRNA in human tumors; however, the exact role of miR‑21‑5p has not been fully determined in endometrial cancer. SRY‑box 17 (SOX17) is associated with endometrial cancer development and progression; however, the regulatory mechanisms underlying SOX17 expression in endometrial cancer remain unclear. In the present study, tumor samples were collected from 160 postmenopausal women with endometrial cancer. All tumor samples were examined for miR‑21‑5p expression by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The results demonstrated that miR‑21‑5p expression was associated with shorter overall survival. In addition, overexpression of miR‑21‑5p promoted epithelial to mesenchymal transition (EMT), whereas silencing miR‑21‑5p reversed EMT in endometrial cancer cell lines. Using RT‑qPCR and western blotting, it was revealed that overexpressing miR‑21‑5p significantly inhibited SOX17 protein expression in endometrial cancer cell lines. Furthermore, as determined by luciferase reporter assay, ectopic expression of miR‑21‑5p inhibited the activity of the SOX17 mRNA 3'‑untranslated region (3'UTR), whereas silencing miR‑21‑5p promoted the activity of the SOX17 mRNA 3'UTR in endometrial cancer cell lines. Overexpression of SOX17 promoted mesenchymal to epithelial transition, whereas silencing SOX17 induced EMT in endometrial cancer cell lines. In addition, tumor SOX17 expression was associated with better overall survival. Therefore, it may be concluded that miR‑21‑5p promotes EMT by targeting SOX17 in human endometrial cancer.Emerging evidence suggests that long non‑coding RNAs (lncRNAs) play pivotal roles in cancer progression, including in intrahepatic cholangiocarcinoma (IHCC). The overexpression of lncRNA ZEB1 antisense 1 (ZEB1‑AS1) has been discovered in several types of cancer; however, the clinical significance and functional role of ZEB1‑AS1 in IHCC have not yet been determined. In the present study, ZEB1‑AS1 was found to be upregulated in IHCC cell lines and tissues. A high ZEB1‑AS1 expression was associated with clinical progression and a poor survival of patients with IHCC, and was identified as an independent risk factor for a poor prognosis. see more In addition, ZEB1‑AS1 promoted the proliferation and metastasis of IHCC cells both in vitro and in vivo. ZEB1‑AS1 was demonstrated to increase the expression of ZEB1 by sponging miR‑200a and to thereby accelerate epithelial‑mesenchymal transition (EMT). On the whole, the findings of the present study demonstrate that ZEB1‑AS1 promotes proliferation and metastasis in IHCC, and induces EMT through the miR‑200a/ZEB1 signaling pathway. ZEB1‑AS1 may thus be a promising prognostic biomarker and essential therapeutic target for IHCC.Non‑small cell lung carcinoma (NSCLC) accounts for 85% of all lung cancers and the five‑year survival rate is ~1% in the late stage. Circular RNAs (circRNAs) were reported to be involved in the progression of diverse human cancers. However, the role of circ‑ACACA in NSCLC progression remains elusive. Quantitative polymerase chain reaction was conducted to detect the expression levels of circ‑ACACA and microRNA (miR)‑1183 in NSCLC tissues and cells. A Cell Counting Kit‑8 assay and transwell assay were employed to check proliferation and migration, respectively. Metabolic alternations in NSCLC cells were monitored by the Seahorse XFe96 analyzer. The protein levels of cellular myelocytomatosis, matrix metallopeptidase 9, glucose transporter 1, phosphatase and tensin homolog, phosphoinositide 3‑kinases (PI3K), phosphorylated PI3K (p‑PI3K), protein kinase B (PKB) and p‑PKB in samples were measured by western blotting. The interaction between circ‑ACACA and miR‑1183 was predicted by circular RNA Interactome, which was verified by dual‑luciferase reporter assay, RNA immunoprecipitation assay and RNA pull‑down assay. Xenograft tumor model was established to investigate the biological roles of circ‑ACACA in vivo. The level of circ‑ACACA was markedly upregulated in NSCLC tissues and cells, which was contrary to the expression of miR‑1183. Knockdown of circ‑ACACA inhibited proliferation and migration of NSCLC cells and also reduced the glycolysis rate. In addition, miR‑1183 was a target of circ‑ACACA and its downregulation reversed circ‑ACACA silencing‑mediated inhibitory impact on NSCLC progression. Further studies indicated that circ‑ACACA regulated the PI3K/PKB pathway through interacting with miR‑1183 and downregulation of circ‑ACACA suppressed tumor growth. Knockdown of circ‑ACACA impeded NSCLC progression by sponging miR‑1183 and inactivating the PI3K/PKB signaling pathway.