STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells via mTOR signal-mediated inhibition of autophagy.

BACKGROUND: Long noncoding RNAs (lncRNAs) are an important class of functional regulators involved in human cancers development, including gastric cancer (GC). Studying aberrantly expressed lncRNAs may provide us with new insights into the occurrence and development of gastric cancer by acting as oncogenes or tumor suppressors. In this study, we aim to examine the expression pattern of lncRNA HAGLROS in GC and its clinical significance as well as its biological role in tumor progression. METHODS: Bioinformatics analysis and qRT-PCR were performed to detect the relative expression of HAGLROS in GC tissues and cell lines. Gain or loss of function approaches were used to investigate the biological functions of HAGLROS. The effect of HAGLROS on proliferation was evaluated by MTT, colony formation assay and nude mouse xenograft model. Wound healing and Transwell assays were used to study the invasion and migration of GC cells. FISH, RIP, RNA-seq, Luciferase report assays, RNA pulldown and Western blot were fulfilled to measure molecular mechanisms. Results are shown as means ± S.D. and differences were tested for significance using Student's t-test (two-tailed). RESULTS: We screened out HAGLROS, whose expression was significantly increased and correlated with outcomes of GC patients by publicly available lncRNAs expression profiling and integrating analyses. Exogenous down-regulation of HAGLROS expression significantly suppressed the cell proliferation, invasion and migration. Mechanistic investigations showed that HAGLROS was a direct target of transcriptional factor STAT3. Moreover, HAGLROS knockdown decreased mTOR expression and increased autophagy-related genes ATG9A and ATG9B expression. Further investigation showed that HAGLROS regulated mTOR signals in two manners. In the one hand, HAGLROS competitively sponged miR-100-5p to increase mTOR expression by antagonizing miR-100-5p-mediated mTOR mRNA inhibition. On the other hand, HAGLROS interacted with mTORC1 components to activate mTORC1 signaling pathway which was known to be an important negative signal of autophagy. Here activation of mTORC1 signaling pathway by HAGLROS inhibited autophagy, thereby promoted excessive proliferation and maintained the malignant phenotype of GC cells. CONCLUSION: The present study demonstrates that HAGLROS overexpression contributes to GC development and poor prognosis and will be a target for GC therapy and further develop as a potential prognostic biomarker.

Use of taxane-containing induction chemotherapy in combination with concurrent chemoradiotherapy in Chinese patients with locally advanced nasopharyngeal carcinoma: a meta-analysis.

PURPOSE: Taxane-containing induction chemotherapy (IC) regimens in combination with concurrent chemoradiotherapy (CCRT) have been compared with non-taxane-containing IC combined with CCRT in randomized controlled trials (RCTs) in Chinese patients with advanced nasopharyngeal carcinoma (NPC). This meta-analysis aimed to systematically evaluate their clinical efficacy and safety profiling in this ethnic population. METHODS: The electronic databases, PubMed, Embase, MEDLINE, and Chinese Biomedical Database, were searched for eligible studies. The outcomes included overall response rate (ORR), 1-year survival rate, and different types of adverse events. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. RESULTS: A total of 12 RCTs (representing 835 patients) were identified. The pooled analysis showed that taxane-containing regimens had a significant improvement in ORR for nasopharyngeal lesion (OR =4.57, 95% CI =1.14-18.30, P=0.032, z=2.15) but not in cervical lymph nodes (OR =1.23, 95% CI =0.65-2.36, P=0.532, z=0.64) and in 1-year survival rates (OR =1.19, 95% CI =0.10-14.82, P=0.893, z=0.13) compared with non-taxane-containing regimens. Regarding the adverse events and toxicities, grade 3-4 leukopenia and neutropenia were significantly different between the two groups (P<0.001) in favor of the non-taxane-containing regimens, but grade 3-4 vomiting was significantly different between the two groups (P<0.005) in favor of the taxane-containing regimens. CONCLUSION: When combined with CCRT, taxane-containing IC regimens may be more efficient for short-term local control in Chinese patients with locally advanced NPC than the non-taxane-containing IC regimens. Moreover, the major toxic effects, which were bone marrow suppression, could be tolerated by majority of patients. More long-term follow-up and high-quality trials of NPC are needed to validate our findings.

[Changes in the physical growth of children aged 3 to 6 years in urban areas of Lanzhou from 2001 to 2010].

OBJECTIVE: To study changes in the physical growth of preschool children aged 3 to 6 yeas in urban areas of Lanzhou from 2001 to 2010. METHODS: Stratified, randomized, cluster sampling was used to collect physical examination data on children from 35 private and public kindergartens located in different urban areas of Lanzhou in 2001, 2006, and 2010. Changes in physical growth were analyzed using body height, body weight and body mass index (BMI) as main indices. Growth retardation, underweight, overweight, emaciation and obesity were screened out using height for age (HAZ), weight for age (WAZ), and weight for height (WHZ) and changes from 2001 to 2010 were analyzed. RESULTS: Body height, body weight and BMI increased from 2001 to 2010 in children at different ages (P<0.05). Body height and weight increased with age, while BMI decreased with age. Mean values of HAZ, WAZ, and WHZ increased over time, showing that prevalence rates of underweight, growth retardation, and emaciation decreased from 2001 to 2010 while those of overweight and obesity increased. CONCLUSIONS: Changes in the physical growth of preschool children in urban areas of Lanzhou from 2001 to 2010 were obvious, with increases in body height and body weight. However, problems such as overweight and obesity emerged. In response, while malnutrition is being solved, attention should be paid to over-nutrition that has an adverse effect on physical growth.

Phosphatase and tensin homolog expression related to cetuximab effects in colorectal cancer patients: a meta-analysis.

AIM: To investigate the correlation between expression of phosphatase and tensin homolog (PTEN) and cetuximab effects in colorectal cancer. METHODS: We searched PubMed, EMBASE and ASCO to identify eligible studies. Finally, 8 randomized control studies were included in the meta-analysis. STATA 10.0 Software was used to investigate heterogeneity among individual studies and to summarize all the studies. Risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS: Compared with 20 of 266 patients with loss of PTEN, 206 of 496 patients with intact PTEN protein expression had a better objective response rate to cetuximab-based therapy (RR, 4.75; 95% CI, 2.59-8.72; P < 0.001). PTEN positivity was associated with better progression-free survival (PFS) (HR, 0.675; 95% CI, 0.473-0.964; P = 0.031) but not with better overall survival (OS) (HR, 0.608; 95% CI, 0.411-0.899; P = 0.013). In patients with KRAS wild-type status, PTEN positivity did not predict a longer PFS or OS (PFS: HR, 0.707; 95% CI, 0.440-1.138; P = 0.154; OS: HR, 0.943; 95% CI, 0.646-1.377; P = 0.761). CONCLUSION: Expression of PTEN is related to the effect of cetuximab in colorectal cancer patients and should be considered in treatment with cetuximab.

Irinotecan-involved regimens for advanced gastric cancer: a pooled-analysis of clinical trials.

AIM: To assess the efficiency and toxicities of irinotecan (CPT-11)-involved regimens in patients with advanced gastric cancer. METHODS: Randomized phases II and III clinical trials on chemotherapy for advanced gastric cancer were searched from MEDLINE, EMbase, Cochrane Controlled Trials Register, and EBSCO. Relevant abstracts were manually searched. A total of 657 patients were analyzed for their overall response rate (ORR), time to treatment failure (TTF), overall survival (OS) rate, and toxicities. Overall survival rate, reported as hazard ratio (HR) with 95% CI, was used as the primary outcome measure. RESULTS: Four randomized controlled trials on chemotherapy for advanced gastric cancer were detected. The CPT-11-containing combination chemotherapy was not significantly advantageous over the non CPT-11-containing combination chemotherapy for OS rate (HR = 1.12, 95% CI: 0.92-1.36, P = 0.266) and ORR [risk ratio (RR) = 1.23, 95% CI: 0.71-2.14, P = 0.458]. However, the CPT-11-containing combination chemotherapy was significantly advantageous over the non CPT-11-containing combination chemotherapy for TTF (HR = 1.35, 95% CI: 1.12-1.64, P = 0.002). Grade 3/4 haematological toxicity (thrombocytopenia: RR = 0.20, 95% CI: 0.09-0.48; P < 0.001) and gastrointestinal toxicity (diarrhea: RR = 4.09, 95% CI: 2.42-6.93, P < 0.001) were lower in patients with advanced gastric cancer after CPT-11-containing combination chemotherapy than after non CPT-11 -containing combination chemotherapy. CONCLUSION: CPT-11-containing combination chemotherapy is advantageous over non CPT-11 -containing combination chemotherapy for TTF with no significant toxicity. CPT-11-containing combination chemotherapy can be used in treatment of advanced gastric cancer.