LncRNA SLC7A11-AS1 promotes the progression of hepatocellular carcinoma by mediating KLF9 ubiquitination.

Hepatocellular carcinoma (HCC) is a malignant tumor, which seriously threatens the life of patients. LncRNA SLC7A11-AS1 was reported to be abnormally expressed in HCC. Here, the functions and relative molecular regulatory mechanism of SLC7A11-AS1 in HCC were investigated. Nude mice and HCC cells were used as the experimental subjects. Knockdown or overexpression of exogenous genes was conducted in HCC cells. RT-qPCR, IHC, and western blot were employed to evaluate the abundance of genes and proteins. The malignant behaviors were evaluated using CCK-8, clone formation, wound-healing, and Transwell. The locations of SLC7A11-AS1 and KLF9 in cells were determined by FISH and IF assays. The total m6A level was evaluated by dot-blot assay. m6A modification of SLC7A11-AS1 was detected using RNA MeRIP. The interactions among molecules were validated by RIP, ChIP, dual luciferase reporter assay, and co-IP. SLC7A11-AS1 was elevated apparently in HCC cells and HCC tissues from mice. SLC7A11-AS1 silencing could suppress HCC progression, which was validated in in vivo and in vitro experiments. Furthermore, METTL3 mediated m6A modification of SLC7A11-AS1 to elevate its expression. In addition, SLC7A11-AS1 downregulated KLF9 expression by affecting STUB1-mediated ubiquitination degradation and KLF9 enhanced PHLPP2 expression to inactivate the AKT pathway. Eventually, rescue experiments revealed that KLF9 knockdown abolished SLC7A11-AS1 silencing-mediated suppression of HCC progression in vivo and in vitro. Our results unveiled that m6A-modified SLC7A11-AS1 promoted HCC progression by regulating the STUB1/KLF9/PHLPP2/AKT axis, indicating that targeting SLC7A11-AS1 might alleviate HCC progression.

Hepatic portal venous gas complication associated with the thoracic endovascular aortic repair for aortic dissection: a case report and literature review.

Aortic dissection (AD) is a serious disease with a higher mortality. The thoracic endovascular aortic repair (TEVAR) is a first line regimen for aortic dissection. Hepatic portal venous gas (HPVG) is a rare disease, and its definite mechanism is unknown. This is a rare association between the aortic and HPVG. In the present report, we present a case of thoracic aortic dissection, which was the type of Standford B by the computer tomography (CT) angiography, which implicated acute abdominal pain and abdominal distention after TEVAR and immediate abdominal CT shown hepatic portal venous gas (HPVG). The patient, who was treated with conservative treatment of gastrointestinal decompressing, fluid resuscitation, electrolyte replacement, anti-infection, anti-inflammation and anticoagulation, was recovered and discharged without abnormalities. This patient has been followed up for 5 years and has not experienced any physical discomfort related to HPVG. This is the first report that the aortic dissection patient implication with HPVG after thoracic endovascular aortic repair.

A combination of transcriptome and methylation analyses reveals the role of lncRNA HOTAIRM1 in the proliferation and metastasis of breast cancer.

Background: DNA methylation status is strongly associated with the prognosis of breast invasive carcinoma (BRCA). Elucidating the mechanisms underlying DNA methylation coupled with determining its biological function is imperative to the effective development of treatment and prevention strategies for breast cancer. Methods: We retrieved transcriptome and DNA methylation profiles of BRCA patients from The Cancer Genome Atlas (TCGA) database, then applied the "limma" package in R software to identify differentially expressed genes (DEGs) and aberrantly methylated genes. Next, we used the "MethylMix" package to screen for methylation-driven genes, and performed univariate and multivariate Cox regression analyses to determine the prognostic value of the methylation-driven genes and clinical characteristics. We validated these findings in 51 breast cancer tissues alongside 51 corresponding normal tissues. Furthermore, we used cell experiments to clarify the biological function and underlying molecular mechanisms of HOTAIRM1 in vitro. Results: A total of 25 methylation-driven genes were identified in the dataset. Results from univariate and multivariate Cox regression showed that SYN2, HOTAIRM1, BCAS1, and ALDOC were significantly associated with patient prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) results showed that the expression levels of SYN2 and HOTAIRM1 were negatively correlated with BRCA stage, whereas those of BCAS1 and ALDOC were positively correlated with BRCA stage. Results from in vitro experiments showed that knockdown HOTAIRM1 expression promoted breast cancer cells proliferation, clone formation, and invasion. Up-regulation of HOTAIRM1 inhibited breast cancer cells proliferation, clone formation, and invasion. Conclusions: In summary, low HOTAIRM1 expression is a significant prognostic factor for the survival of BRCA patients and thus could be a potential therapeutic target for the treatment of BRCA.

A Competing Endogenous RNA Network Reveals Novel lncRNA, miRNA and mRNA Biomarkers With Diagnostic and Prognostic Value for Early Breast Cancer.

BACKGROUND: This study aims to reveal early breast cancer (BC) specific competing endogenous RNA (ceRNA) network through the expression profiles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and mRNAs. METHODS: Based on The Cancer Genome Atlas (TCGA), we obtained the differentially expressed mRNAs, miRNAs, and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) between early BC and normal samples. The lncRNA-miRNA-mRNA interaction network was constructed using Cytoscape. Functional enrichment were performed using GeneCoDis3. The expression of selected genes were validated by qRT-PCR. Based on the published dataset, we validated the result of TCGA integration analysis. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively. RESULTS: Totally, 1207 DEmRNAs, 194 DElncRNAs and 37 DEmiRNAs were obtained. Functional enrichment analysis results showed that all of DEmRNAs were enriched in pathway of cytokine-cytokine receptor interaction, PPAR signaling pathway and pathways in cancer. The DEmRNA-DEmiRNA-DElncRNA interaction network in early BC was consisted of 23 DEmiRNAs, 95 DElncRNAs and 309 DEmRNAs. Among ceRNA network, IL-6-hsa-miR-182-5p-ADAMTS9-AS1 interactions, LIFR-hsa-miR-21-5p-ADAMTS9-AS1 interactions and MMP1/MMP11-hsa-miR-145-5p-CDKN2B-AS1 interactions were speculated to involve in the development of early BC. The qRT-PCR results were consistent with our integrated analysis. Except for ADAMTS9-AS1 and CDKN2B-AS1, expression of the others results in the Gene Expression Omnibus (GEO) dataset were generally consistent with TCGA integrated analysis. The area under curve (AUC) of the ADAMTS9-AS1, CDKN2B-AS1, IL-6, MMP11, hsa-miR-145-5p and hsa-miR-182-5p were 0.947, 0.862, 0.842, 0.993, 0.960 and 0.944, and the specificity and sensitivity of the 6 biomarkers were 83.4% and 95.6%, 72.2% and 90.3%, 80.1% and 74.3%, 96.2% and 96.5%, 90.1% and 92.3%, and 88.7% and 90.4%, respectively. In addition, IL-6 had potential prognostic value for early BC. CONCLUSION: These findings may provide novel insights into the lncRNA-miRNA-mRNA network and uncover potential therapeutic targets in early BC.

The molecular mechanism of breast cancer cell apoptosis induction by absent in melanoma (AIM2).

OBJECTIVE: To determine the molecular mechanism by which absent in melanoma 2 (AIM2) induces breast cancer cell apoptosis. METHODS: Establish Tet-Off(TM) model system to induce AIM2 expression in great quantities, MCF-7 tTA-AIM2 cells were the experimental group; MCF-7 tTA-Luc cells were the control group. The expression and subcellular localization of AIM2 in breast cancer cell lines were determined via Western Blotting. AIM2 protein expression was determined after the addition of interferon-γ (102 U/ml). Flow cytometry was used to analyze the effects of AIM2 on the cell cycle. Apoptosis detection was performed by staining with Annexin V-FITC and propidium iodide. Apoptosis mechanism was detected via Western Blotting. The XTT assay was used to analyze the effects of AIM2 on cell growth. RESULT: This experiment established Tet-Off guidance system. This system results which promotes AIM2 gene transcription and increased AIM2 protein expression. Four days after induction, AIM2 expression was detected. AIM2 expression increased with the number of days post-induction. AIM2 is present in cytoplasm and nuclei. Interferon-γ (102 U/ml) induced AIM2 protein expression and significantly increased AIM2 expression. AIM2 expression had no significant effect on the cell cycle, With the increase of Cdk2 expression induced by days were gradually increased, and Cdk4, Cyclin E expression was no significantly difference. AIM2 expression can significantly promote the apoptosis of breast cancer cells. Increased AIM2 expression can inhibit the expression of the anti-apoptotic protein Bcl-xL, increase the expression of the apoptosis proteins Bad and Bax, and activate caspases, resulting in cleavage of the DNA repair protein PARP. The XTT assay showed that AIM2 expression slows the rate of cell growth. CONCLUSION: In this breast cancer Tet-Off(TM) system, AIM2 was expressed in the cytoplasm and nucleus, stimulated the mitochondria to promote apoptosis, and influenced cell survival and proliferation.

Spontaneous isolated dissection at renal upper abdominal aortic: a rare case report.

Arterial dissection is defined as a cleavage of the arterial wall caused by intramural hematoma. Isolated extra-aortic arterial dissection has been reported in renal and carotid arteries in few literatures but suprarenal aorta dissection associated with retrograde formation of a giant descending thoracic aneurysm is considered very rare. We present a quite unusual case of suprarenal aorta dissection associated with retrograde formation of a giant descending thoracic aneurysm sparing both renal and mesenteric vessels, without any branch vessel involvement or visceral damage. Because of the patient's persistent epigastric pain, endovascular celiac artery stent implantation was performed with 3 multiple overlapping uncovered stents. Twelve months after the procedure, computed tomographic angiography (CTA) of the abdomen showed patency of both celiac stents with thrombus formation in the retrograde dissection sac, and the patient remained asymptomatic. This case and others in the medical literature suggest that endovascular treatment can be feasible in symptomatic patients with spontaneous isolated dissection at renal upper abdominal aortic.

Midazolam inhibits the proliferation of human head and neck squamous carcinoma cells by downregulating p300 expression.

The objective of this study was to investigate the mechanism of midazolam in inhibiting the proliferation of hypopharyngeal squamous carcinoma cells. Cultured FaDu cancer cells were treated with different concentrations of midazolam. MTT and BrdU incorporation assays were then used to evaluate cancer cell proliferation. The mRNA and protein levels of p300, a key factor involved in the tumorigenesis of numerous cancers, were measured with RT-PCR and Western blotting, respectively. Midazolam inhibited the expression of p300 and the proliferation of FaDu cells. Additionally, knockdown of p300 resulted in increased expression of p21 and p27 and decreased expression of p-Rb while inhibiting the proliferation of FaDu cells. Midazolam inhibits the proliferation of human head and neck squamous carcinoma cells by downregulating p300. Midazolam may be useful for the treatment of hypopharyngeal squamous cancers.

A rapidly progressive giant tumor with one year growth on breast: a rare size breast mass.

Primary rapidly progressive malignant tumor on breast is a very rare disease. We report a 62-year-old postmenopausal patient with history of one year breast lump and progressive increase in a period of two months. The giant breast tumor with a rare size about 7.5 × 7.0 cm, the skin of the breast to become resembling orange peel and metastasis to multiple organs. The histological sections of core needle biopsy confirmed the diagnosis of invasive adenocarcinoma. Hence, reduction surgery for local skin in the treatment of breast cancer increased the effectiveness of the docetaxel epirubicin (TE: docetaxel 75 mg/m(2), day 1; epirubicin 75 mg/m(2), day 1) chemotherapy by improving the patient's general condition, and not continue to increase was observed during follow-up.