TMEM161B-AS1 suppresses proliferation, invasion and glycolysis by targeting miR-23a-3p/HIF1AN signal axis in oesophageal squamous cell carcinoma.

Mounting data have shown that long non-coding RNAs (lncRNAs) widely participate in tumour initiation, development, progression and glycolysis in a variety of tumours. However, the clinical prognosis and molecular mechanisms of TMEM161B-AS1 in oesophageal squamous cell carcinoma (ESCC) remain still unknown. Here, TMEM161B-AS1 and HIF1AN were significantly lower in ESCC tissues than in normal samples, and their low expressions were both related to TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Functionally, TMEM161B-AS1 overexpression or miR-23a-3p depletion suppressed the proliferation, invasion and glycolysis as well as reduced glucose consumption and lactate production in ESCC cells. Mechanistically, TMEM161B-AS1 manipulated HIF1AN expression by competitively sponging miR-23a-3p in ESCC cells. MiR-23a-3p mimic and HIF1AN siRNA partly reversed cell phenotypes mediated by TMEM161B-AS1 in ESCC cells. Collectively, TMEM161B-AS1, miR-23a-3p and HIF1AN may be tightly involved in ESCC development and progression as well as patients' prognosis, and TMEM161B-AS1/miR-23a-3p/HIF1AN signal axis may be a promising target for the treatment of ESCC patients.

TKTL1 expression and its downregulation is implicated in cell proliferation inhibition and cell cycle arrest in esophageal squamous cell carcinoma.

It is well known that tumor cells mainly depend on the nonoxidative pathway of the pentose phosphate pathway (PPP), and transketolase-like 1 (TKTL1), a kind of crucial metabolism enzyme, participates in the regulation of PPP; notably, overwhelming evidence has demonstrated that TKTL1 plays pivotal roles in the development and progression of multiple tumors. However, there were no reports about the role of TKTL1 in esophageal squamous cell carcinoma (ESCC). Here, we investigated TKTL1 expression and preliminarily elucidated its underlying biological functions in ESCC. We found that TKTL1 exhibited the high expression in ESCC tissues and cells, and the survival rate of patients with negative TKTL1 expression was significantly higher than that of patients with positive TKTL1 staining (P < 0.05). Additionally, significant correlations of TKTL1 expression with histologic grade, clinical stage, and lymph node metastasis were found (P < 0.05). Subsequently, TKTL1 small interfering RNA (siRNA) significantly reduced TKTL1 messenger RNA (mRNA), and protein levels companied with the marked reduce of total transketolase activity but did not affect TKT and TKTL1 mRNA level. More importantly, TKTL1 siRNA obviously induced cell cycle arrest in G0/G1 phase and suppressed cell proliferation in vitro and in vivo coupled with the reduced cyclin D1 and cdk4 levels as well as decrease of Ki-67 proliferation index in EC1 cells. Taken altogether, our results suggest that TKTL1 as a key prognostic factor may be a novel target for therapy of the patients with ESCC.

Long non-coding RNA XIST contributes to osteoarthritis progression via miR-149-5p/DNMT3A axis.

Long non-coding RNAs (lncRNAs) are largely involved in the development of osteoarthritis (OA), a chronic and degenerative joint disease. The objective of this paper is to research the functional role and molecular mechanism of lncRNA X inactive specific transcript (XIST) in OA. The levels of XIST, microRNA-149-5p (miR-149-5p), and DNA methyltransferase 3A (DNMT3A) were measured. Cell viability and apoptosis rate were determined. Associated protein levels were examined through Western blot. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were implemented for confirming the target relation. And the role of XIST on OA in vivo was investigated by a rat model. XIST was expressed at a high level in OA cartilage tissues and IL-1ß-treated chondrocytes. XIST knockdown promoted cell viability but restrained cell apoptosis and extracellular matrix (ECM) protein degradation in IL-1ß-treated chondrocytes. XIST directly targeted miR-149-5p and miR-149-5p down-regulation restored si-XIST-mediated pro-proliferative and anti-apoptotic or ECM degradative effects. DNMT3A was a target gene of miR-149-5p and DNMT3A overexpression ameliorated miR-149-5p-induced promotion of cell viability but repression of apoptosis and ECM degradation. Knockdown of XIST reduced DNMT3A level by motivating miR-149-5p expression. The inhibitory influence of XIST down-regulation on OA evolvement was also achieved by miR-149-5p/DNMT3A axis in vivo. In a word, knockdown of XIST can repress the development of OA by miR-149-5p/DNMT3A axis. This study discovers the XIST/miR-149-5p/DNMT3A axis in regulating OA evolution, which is beneficial for understanding the molecular pathomechanism and can lay a good foundation for targeted therapy of OA treatment.

UBE2C is involved in the functions of ECRG4 on esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancerrelated gene 4 (ECRG4) is down-regulated in esophageal squamous-cell carcinoma (ESCC) and inhibits the tumorigenicity of ESCC cells. Ubiquitin conjugating enzyme E2 (UBE2C), an E2 ubiquitin-conjugating enzyme, is upregulated in numerous human cancers, including ESCC. METHODS: mRNA and protein expression was determined by real-time PCR and western blotting analysis, respectively. Cell apoptosis was assessed by Annexin V-fluorescein isothiocyanate staining and flow cytometry analysis. RESULTS: By analyzing previous quantitative proteomics data on EC9706 cells, we found that UBE2C was significantly down-regulated in ECRG4 overexpressed cells. Western blotting analysis validated the proteomics results in both EC9706 and EC-18 cells. In addition, Pearson's correlation analysis demonstrated a negative correlation between the mRNA levels of ECRG4 and UBE2C in ESCC tissues. Then, we found that Nuclear Factor-κB (NF-κB) inhibitor, pyrriolidine-dithiocarbamate (PDTC), could inhibit NF-κB p65 nuclear translocation and UBE2C expression, which was partially reversed by ECRG4 silence. More importantly, UBE2C knockdown in TE-1 cells significantly inhibited cell proliferation and induced cell apoptosis, which was partially reversed by ECRG4 knockdown. CONCLUSIONS: ECRG4 down-regulated UBE2C expression in ESCC cells via NF-κB signaling. UBE2C was involved in the anti-proliferative and pro-apoptotic functions of ECRG4 in ESCC cells.

[Value of Glasgow prognostic score in patients with adenocarcinoma of esophagogastric junction].

OBJECTIVE: To evaluate the prognosis and predictive values of preoperative Glasgow prognostic score (GPS) for adenocarcinoma of esophagogastric junction(AEG) patients. METHODS: A retrospective study of 322 AEG patients who received operation between January 2007 and March 2010 in Henan Provincial People's Hospital was performed. Clinical data, pathological characteristics, laboratory parameters and survival data were collected. The GPS was calculated based on C-reactive protein(CRP) and serum albumin(ALB) levels. Univariate and multivariate analysis were used to evaluate the prognostic value of GPS. RESULTS: Among 322 patients, 0, 1, 2 of GPS were 192, 104 and 26 patients respectively. The median follow-up was 37 (4-73) months. In Kaplan-Meier analysis, median diseases-free survival (DFS) of GPS 0, 1, 2 was 47.0 (95% CI: 31.6-62.4), 15.0 (95% CI: 11.8-8.2) and 4.7 (95% CI: 3.8-5.6) months (P<0.01), and median overall survival (OS) was out of reach, 20.6 (95% CI: 15.8-25.4) and 7.0 (95% CI: 5.8-8.2) months (P<0.01). Univariate and multivariate analysis revealed that GPS was an independent predictor of DFS (P<0.01) and OS (P<0.01) of AEG. CONCLUSION: GPS is an effective predictor of survival in AEG.