IntroductionLong non-coding RNAs (lncRNAs) have obtained increasing attention due to their regulatory functions in many cancers. This work aimed to investigate the functional roles of lncRNA TTN-AS1 in colorectal cancer (CRC) and to explore the underlying mechanisms.MethodsThe expression profiles of TTN-AS1 and miR-497 in CRC tissues and cell lines were determined by RT-qPCR analysis. MTT assay, transwell assay, western blot analysis, and xenograft tumors in nude mice were employed to analyze the effects of TTN-AS1 on the proliferation, migration, invasion, EMT, and in vivo tumorigenesis of CRC cells. Bioinformatics analysis and dual-luciferase reporter assay determined the direct binding relation between TTN-AS1 and miR-497 in CRC.ResultsWe observed a significant increase of TTN-AS1 expression level in CRC tissues and cell lines compared with normal counterparts. High expression of TTN-AS1 predicted a poor prognosis and was correlated with aggressive clinicopathological characteristics in CRC patients. Functionally, gain- and loss-of-function studies indicated that TTN-AS1 knockdown suppressed the proliferation, migration, invasion and epithelial–mesenchymal transition of CRC cells in vitro, whereas TTN-AS1 overexpression showed the complete opposite effects. Mechanistically, we found that TTN-AS1 could directly interact with miR-497, and co-transfection with miR-497 mimics blocked the activation of PI3K/Akt/mTOR signaling, and reversed the effects of TTN-AS1 overexpression in CRC cells.ConclusionTo conclude, our findings provide novel insight into CRC tumorigenesis and indicate that TTN-AS1 may serve as a potential therapeutic target for CRC treatment.
In Syrian hamster embryo (SHE) fibroblasts, epidermal growth factor receptor (EGFR) tyrosine kinase activity regulates the metabolism of endogenous linoleic acid to (13S)-hydroperoxyoctadecadienoic acid (13S)-HPODE). (13S)-HPODE stimulates EGF-dependent mito-genesis in a SHE cell phenotype, which expresses tumor suppressor genes (supB ؉ ), but was not effective in a variant that does not express these suppressor genes (supB ؊ ). In the present study, we have investigated the potential effects of this lipid metabolite on the EGFR signaling pathways in these two SHE cell lines. Treatment of quiescent SHE cells with EGF produced a rapid, transient increase in the tyrosine phosphorylation of EGFR. Dependence on EGF concentration for EGFR tyrosine phosphorylation was similar in both SHE cell lines, but a more prolonged phosphorylation was detected in the supB ؊ variant. Incubation of supB ؉ cells with (13S)-HPODE and EGF increased EGFR autophosphorylation and tyrosine phosphorylation on several signaling proteins with Src homology-2 domains including GTPase-activating protein. The lipid metabolite did not significantly alter EGF-dependent tyrosine phosphorylation in the supB ؊ variant. Tyrosine phosphorylation of mitogen-activated protein (MAP) kinase was also measured. The addition of (13S)-HPODE increased the extent and duration of MAP kinase tyrosine phosphorylation in supB ؉ cells but not in the supB ؊ variant. MAP kinase activity in supB ؉ cells, as measured in immunoprecipitates from cells after the addition of EGF, was increased by the presence of (13S)-HPODE. The addition of (13S)-HPODE did not directly alter EGFR kinase activity or the internalization of the EGFR. However, the addition of (13S)-HPODE to supB ؉ cells extended the tyrosine phosphorylation of the EGFR in response to EGF. The dephosphorylation of the EGFR was measured directly, and a slower rate was observed in the supB ؊ compared with the supB ؉ cells. Incubation of the supB ؉ cells with (13S)-HPODE attenuated the dephosphorylation of the EGFR. Thus, (13S)-HPODE stimulates EGF-dependent mitogenesis and up-regulation of EGF-dependent tyrosine phosphorylation by inhibiting the dephosphorylation of the EGFR. This study shows that a metabolite of an essential dietary fatty acid, linoleic acid, can modulate tyrosine phosphorylation and activity of key signal transduction proteins in a growth factor mitogenic pathway.Several lines of evidence suggest that metabolism of the cis-polyunsaturated fatty acids, arachidonic acid and linoleic acid, by prostaglandin H synthase and lipoxygenases generate metabolites that modulate the EGF 1 mitogenic signal in fibroblasts. In Balb/c 3T3 fibroblasts, mitogenic stimulation by EGF induced the formation of prostaglandin E 2 (1) and the expression of c-myc (2). Inhibition of prostaglandin H synthase partially blocked both mitogenesis and c-myc expression, which was restored and enhanced by the addition of exogenous prostaglandins. In these studies lipoxygenase inhibitors were very effective inhibitors of mitogenesis...
Berberine is sourced from multiple medicinal herb resources and is easy to extract. With the advantages of low price, safety and convenience, berberine may have potential for wide clinical use. The present study aimed to investigate whether berberine inhibited the viability of colon cancer and whether it regulated the three-gene network microRNA (miR)-21-integrin β4 (ITGβ4)-programmed cell death 4 (PDCD4). It was demonstrated that berberine treatment suppressed colon cancer cell viability, and induced apoptosis and activated caspase-3 activity in the human colon carcinoma HCT116 cell line. Berberine inhibited miR-21 expression and promoted ITGβ4 and PDCD4 protein expression in the HCT116 cell line. Overexpression of miR-21 reduced the anti-cancer effects of berberine on cell viability, apoptosis rate and caspase-3 activity of the HCT116 cell line. However, it was revealed that the overexpression of miR-21 also suppressed ITGβ4 and PDCD4 protein expression in the HCT116 cell line. In conclusion, miR-21, ITGβ4 and PDCD4 are involved in the anti-cancer effects of berberine on cell viability and apoptosis in the HCT116 cell line.
Objective To assess three‐dimensional (3D) ultrasound combined with power Doppler (PD) for the differential diagnosis of endometrial lesions among infertile women. Methods A prospective study carried out at a reproductive medicine center in Luoyang, China, between January and December 2015. The inclusion criteria were asymptomatic infertility with normal endometrium or specific endometrial lesions. Participants were subdivided by whether they had normal endometrium (group 1, n=357), or endometrial lesions including polyps, hyperplasia, intrauterine adhesions, or endometritis (group 2, n=99). 3D PD and hysteroscopy were performed in the follicular phase. Endometrial thickness, volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI), and subendometrial VI, FI, and VFI were calculated. Endometrial lesions were confirmed by pathologic analysis. Results The overall prevalence of endometrial lesions was 99/456 (21.3%). Endometrial thickness and volume were significantly larger in group 2 than in group 1 (9.96 ± 3.24 vs 8.15 ± 2.50 mm and 3.70 ± 2.54 vs 2.42 ± 1.64 cm3, respectively; both P<0.001). Endometrial thickness and volume were larger among women with endometrial polyps and hyperplasia; endometrial VI, FI, and VFI were lower among women with intrauterine adhesions. Conclusion Three‐dimensional PD has value for the differential diagnosis of endometrial lesions among infertile women. Clinical trial registration The trial is registered in the Chinese Clinical Trial Registry as ChiCTR1800015799.
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