Long Noncoding RNA CBR3-AS1 Promotes Stem-like Properties and Oxaliplatin Resistance of Colorectal Cancer by Sponging miR-145-5p.

Accumulating articles indicate that long noncoding RNAs (lncRNAs) serve as essential regulators in a plethora of human cancers. In this study, we analyzed the expression profile and functional role of lncRNA CBR3-AS1 in colorectal cancer (CRC). High-expression levels of CBR3-AS1 were found in CRC tissues and cell lines. Upregulated CBR3-AS1 was closely associated with poor prognosis and adverse clinicopathological features of CRC patients. Artificial knockdown of CBR3-AS1 markedly suppressed the proliferation, migration, invasion, and stem-like properties but promoted the apoptosis of CRC cells. Moreover, we observed that CBR3-AS1 could directly bind to miR-145-5p and negatively regulated its expression in CRC. Further experiments also demonstrated that inhibition of miR-145-5p reverted the effects of CBR3-AS1 knockdown on CRC cells. In addition, compared with the parental cells, CBR3-AS1 expression was strikingly increased in oxaliplatin- (OXA-) resistant CRC cells, and the OXA resistance was notably diminished by CBR3-AS1 knockdown. To conclude, our study suggested that CBR3-AS1 serves an oncogenic role in CRC and may be exploited as a novel therapeutic target for CRC patients.

LncRNA NEAT1 facilitates pancreatic cancer growth and metastasis through stabilizing ELF3 mRNA.

Recently, increasing evidence has revealed that long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of multiple cancers. Although the oncogenic effects of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in some cancers have been reported, the functional significance and molecular mechanism of NEAT1 in pancreatic cancer (PC) progression remains elusive. In this study, our findings showed that NEAT1 expression was upregulated in PC tissues and cell lines; high NEAT1 expression was associated with tumor size, TNM stage, lymph node and distant metastasis, and also predicted poor prognosis. Functional experiments demonstrated that NEAT1 could promote PC cell proliferation and metastasis both in vitro and in vivo. Mechanistically, NEAT1 could associate with E74 like ETS transcription factor 3 (ELF3) mRNA and enhance the combination of Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and ELF3 mRNA, subsequently suppressing the degradation of ELF3 mRNA. Overall, our research indicates that NEAT1 might be a potential therapeutic target for patients with PC.

HMGB2 promotes the malignancy of human gastric cancer and indicates poor survival outcome.

HMGB2 is an important protein in carcinogenesis. However, little is known about the specific role of HMGB2 in gastric cancer. In the present study, HMGB2 expression was evaluated in 198 primary gastric cancer tissues and their adjacent nontumor controls. The correlation between HMGB2 expression and clinico-pathological features and survival was assessed. The effect of HMGB2 on cell proliferation, invasion, and glycolysis was examined in vitro. The expression of HMGB2 was significantly increased in human gastric cancer when compared with nontumor tissues (P < .001). High HMGB2 expression correlated with large tumor size (P = .001), advanced T stage (P = .007), and presence of lymph node metastasis (P = .004). Moreover, high HMGB2 expression was validated as an independent prognostic factor in both univariate and multivariate analyses (P < .05). Experimentally, silencing HMGB2 expression by stable transfected shRNA significantly decreased the proliferation, invasion, and glycolysis of gastric cancer cells. In conclusion, HMGB2 is a novel prognostic biomarker for survival in gastric cancer, and knockdown HMGB2 expression in gastric cancer cells attenuated proliferation and invasion, and impaired glycolysis in gastric cancer cells. Hence, HMGB2 may serve as a new biomarker and a potential therapeutic target in gastric cancer.

MMP14 predicts a poor prognosis in patients with colorectal cancer.

Matrix metalloproteinases (MMPs) are involved in most biological processes. Recently, MMP14 was reported to be up-regulated in some types of cancer and to promote cancer cell invasion and metastasis. However, there are few reports on the clinical significance of MMP14 in colorectal cancer (CRC). In this study, MMP14 expression was first investigated in The Cancer Genome Atlas (TCGA) and whole-genome expression microarray (GEO; Accession Number GSE39582) and then validated with our database. Univariate and multivariate analyses were performed to assess the association between prognostic factors and survival outcomes. MMP14 was upregulated at both the transcriptional and protein levels in cancer compared with normal tissues (P < .05), and high MMP14 expression was associated with advanced tumor stage in the 3 study cohorts. In the univariate Cox proportional hazard ratio analysis, MMP14 correlated significantly with prognosis in both the TCGA and GSE39582 databases (P < .05). In the validation cohort, patients with high MMP14 expression had lower 5-year disease-free survival (DFS; hazard ratio [HR] 6.707; 95% confidence interval [CI] 3.184, 14.128; P < .001) and overall survival (OS; HR 10.669; 95% CI 3.828, 29.737; P < .001) than those with low MMP14 expression. Multivariate survival analysis showed that MMP14 was an independent prognostic marker for both DFS (HR 5.776; 95% CI 2.719, 12.270; P < .001) and OS (HR 8.971; 95% CI 3.199, 25.156; P < .001). Clearly, MMP14 plays an important role in CRC progression and prognosis and could be a useful biomarker for prediction of survival after colectomy.

Expression of long non-coding RNA PANDAR and its prognostic value in colorectal cancer patients.

BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as key molecules in human cancer. In the present study, we explored the role of the lncRNA PANDAR in colorectal cancer (CRC). METHODS: The relative expression level of lncRNA PANDAR in CRC tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The associations between PANDAR expression and clinicopathological features of CRC patients were further analyzed. Kaplan-Meier survival analysis was performed to evaluate the value of PANDAR in the prognosis of CRC patients. Furthermore, the biological function of PANDAR on CRC cell growth, apoptosis and mobility was investigated through MTT, flow cytometry, transwell migration and invasion assays in vitro. RESULTS: The expression level of PANDAR was higher in CRC tissues and cells compared with adjacent nontumor tissues and normal colonic cell line NCM460. PANDAR expression was significantly correlated with local invasion, lymph node metastasis and TNM stage. Kaplan-Meier analysis showed that patients with high PANDAR expression had poorer overall survival than patients with low PANDAR expression. Multivariate Cox regression analysis indicated that PANDAR might be an independent prognostic factor for CRC patients. Furthermore, PANDAR knockdown significantly inhibited cell proliferation, cycle progression, migration and invasion of CRC in vitro. CONCLUSIONS: Our results suggest that high expression of PANDAR was involved in CRC progression and could act as an independent biomarker for prognosis of CRC patients.