The lncRNA MIR4435-2HG is upregulated in hepatocellular carcinoma and promotes cancer cell proliferation by upregulating miRNA-487a.

BACKGROUND: Given the high mortality rate and unclear pathogenesis for liver cancer, investigation of its molecular mechanisms is essential. We focused on the long non-coding RNA (lncRNA) MIR4435-2HG, which was recently reported to be oncogenic in lung cancer and the microRNA miRNA-487a, which has been reported to be oncogenic in hepatocellular carcinoma (HCC). Our aim was to determine if the former has a role in HCC, and to further validate the role of the latter. METHODS: Samples from 64 patients with HCC were taken at The Third Affiliated Hospital of Sun Yat-Sen University. Cell transfection and PCR were applied. RESULTS: We found that MIR4435-2HG and miRNA-487a were upregulated in tumor tissues compared to adjacent healthy tissues from HCC patients. The expression of MIR4435-2HG was significantly affected by tumor size but not by tumor metastasis. Correlation analysis showed that MIR4435-2HG and miRNA-487a were positively correlated in both the tumor tissues and adjacent healthy tissues from HCC patients. Overexpression of MIR4435-2HG led to upregulation of miRNA-487a in the cells of HCC cell lines, while overexpression of miRNA-487a did not significantly affect MIR4435-2HG. Overexpression of MIR4435-2HG and miRNA-487a promoted the proliferation of cells of HCC cell lines, and miRNA-487a knockdown partially attenuated the enhancing effects of MIR4435-2HG overexpression on cancer cell proliferation. CONCLUSION: MIR4435-2HG is upregulated in HCC and promotes cancer cell proliferation possibly by upregulating miRNA-487a.

miR-1245a promotes the proliferation and invasion of colon adenocarcinoma by targeting BRCA2.

BACKGROUND: Colon adenocarcinoma (CA) is the most common one with poor survival in colon cancer. This study aims to investigate the effect of miR-1245a on the process of CA cells and its target gene BRCA2. METHODS: The expression of CA tissues and cells were evaluated by q RT-PCR. Then we explore the association between expression of miR-1245a and prognosis in the CA patients from the TCGA database. CCK8 assays, colony formation assays were performed to explore the effect of miR-1245a in CA cell proliferation. The invasion ability of CA cells was evaluated by Transwell assays. Western blot was performed to assess the BRCA2 expression. Luciferase reporter assay was employed to scrutinize the relationship between miR-1245a and BRCA2. Finally, rescue experiments were performed through BRCA2 downregulation and miR-1245a inhibitors by using colony formation assay and Transwell invasion assay. RESULTS: miR-1245a is upregulated in CA cells and tissues. Additionally, the high expression of miR-1245a was related to poor survival. CCK8 assays, colony formation assays and Transwell assays showed that miR-1245a promotes the proliferation and invasion of CA cells. The luciferase reporter assay indicated that miR-1245a targeted BRCA2 and inhibited its expression. The rescue experiment further showed that miR-1245a could restore the effect of BRCA2 on CA. CONCLUSIONS: miR-1245a promotes the proliferation and invasion of CA by targeting BRCA2.Our results suggested that miR-1245a could be a potential biomarker for CA progression.

Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson's Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage.

Trefoil factor 3 (TFF3), cholinesterase activity (ChE activity) and homocysteine (Hcy) play critical roles in modulating recognition, learning and memory in neurodegenerative diseases, such as Parkinson's disease dementia (PDD) and vascular parkinsonism with dementia (VPD). However, whether they can be used as reliable predictors to evaluate the severity and progression of PDD and VPD remains largely unknown. METHODS: We performed a cross-sectional study that included 92 patients with PDD, 82 patients with VPD and 80 healthy controls. Serum levels of TFF3, ChE activity and Hcy were measured. Several scales were used to rate the severity of PDD and VPD. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of PDD and VPD patients compared to healthy subjects. RESULTS: Compared with healthy subjects, the serum levels of TFF3 and ChE activity were lower, while Hcy was higher in the PDD and VPD patients. These findings were especially prominent in male patients. The three biomarkers displayed differences between PDD and VPD sub-groups based on genders and UPDRS (III) scores' distribution. Interestingly, these increased serum Hcy levels were significantly and inversely correlated with decreased TFF3/ChE activity levels. There were significant correlations between TFF3/ChE activity/Hcy levels and PDD/VPD severities, including motor dysfunction, declining cognition and mood/gastrointestinal symptoms. Additionally, ROC curves for the combination of TFF3, ChE activity and Hcy showed potential diagnostic value in discriminating PDD and VPD patients from healthy controls. CONCLUSIONS: Our findings suggest that serum TFF3, ChE activity and Hcy levels may underlie the pathophysiological mechanisms of PDD and VPD. As the race to find biomarkers or predictors for these diseases intensifies, a better understanding of the roles of TFF3, ChE activity and Hcy may yield insights into the pathogenesis of PDD and VPD.

LncRNA XIST functions as a molecular sponge of miR-194-5p to regulate MAPK1 expression in hepatocellular carcinoma cell.

Increasing evidence highlights the important role of XIST, a long non-coding RNA (lncRNA), in the regulation of multiple cancers. However, the underlying mechanism of XIST in human hepatocellular carcinoma (HCC) still remains to be explored. Herein, intended to investigate the functional role of XIST in HCC initiation and progression. We first detected that XIST was significantly upregulated in HCC tissues and associated with tumor size and vascular invasion. Gain- and loss-of-function of XIST further presented that XIST promoted the progression of HCC cells, including proliferation, migration, and invasion. Moreover, silencing of XIST could inhibit tumor growth in vivo. We also found that XIST could target miR-194-5p and thus decrease miR-194-5p expression. Besides that, restoring XIST could reverse the inhibitory effect of miR-194-5p on the proliferation and invasion of HCC cells. We further elucidated such rescue role might through derepressing MAPK1 expression, the target of miR-194-5p. In brief, the above results elucidate the important role of XIST in HCC tumorigenesis, suggesting that XIST might be a candidate prognostic biomarker and a novel therapeutic target for treating HCC.

Molecular epidemiology of aminoglycosides resistance on Klebsiella pneumonia in a hospital in China.

To investigate the molecular epidemiology of aminoglycosides resistance among Klebsiella pneumonia in hospitals in China, the antibiotics resistance and the possession of extended-spectrum ß-lactamases (ESBLs) from 162 isolates were examined using Kirby-Bauer disk diffusion and PCR sequencing. Overall, 47.5% (77/162) of strains showed an ESBL phenotype. According to antibiotics resistance, ESBLs-positive K. pneumoniae showed significantly higher resistance to most antibiotics than ESBLs-negative strains (P<0.05). Moreover, 162 strains harboured aminoglycoside-modifying enzymes genes (AMEs) including aac (3)-II (n = 49), aac (6')-Ib (n = 32), ant (3")-I (n = 22) and ant (2")-I (n = 7). Overall, 11.1% (18/162) and 6.2% (10/162) of isolates carried 16S rRNA methylase genes (armA and rmtB), in which the aminoglycoside MIC was more than 256 µg/ml. In conclusion, our study characterised aminoglycosides resistance among K. pneumoniae strains in China hospitals and revealed antibiotic resistance and the increased presence of AMEs and 16S rRNA methylase genes in K. pneumonia, enabling the prevalence of aminoglycosides resistance of K. pneumoniae to be tracked from patients.

Prevalence and fluoroquinolone resistance of pseudomonas aeruginosa in a hospital of South China.

Pseudomonas aeruginosa is an opportunistic pathogen that poses a threat in clinical settings. This study aimed to investigate the molecular characterization and epidemiology of fluoroquinolones (FQs) resistance in P. aeruginosa isolated from South China. A total of 256 P. aeruginosa strains isolated from outpatients, emergency patients and inpatients were collected from January 2010 to December 2010 in the hospital of South China. The resistance profile of all isolated strains was screened by antibiotic-susceptibility testing, and the molecular characteristics of plasmid-mediated quinolone resistance (PMQR) and the quinolone resistance determining region (QRDR) were determined using PCR in combination with DNA sequencing. The result of antibiotic-susceptibility tests showed that most strains were sensitive to polymyxin B, piperacillin, piperacillin/tazobactam, ceftazidime and amikacin. Moreover, 65 isolates were identified as resistant to ciprofloxacin. Further analysis of QRDR revealed that the resistant strains carried at least one mutation in the gyrA (The83Ile), gyrB (Ser467Phe, Gln468His) and parC (Ser87Leu) genes, but no mutation was detected in parE. For the first time, we report here that the qnrA1 gene is associated with low levels of resistance to ciprofloxacin from clinical P. aeruginosa isolates in South China. The mutation of gyrA (at position 83) is clearly linked to the FQs resistance of P. aeruginosa. Moreover, FQs resistance of P. aeruginosa may be due to the chromosome-mediated resistance mechanism rather than PMQR.