LINC00511-dependent inhibition of IL-24 contributes to the oncogenic role of HNF4α in colorectal cancer.

Hepatocyte nuclear factor 4 α (HNF4α) is an important transcription factor that acts as a pro-proliferative mediator during tumorigenesis, yet its function in colorectal cancer (CRC) remain unclear. Hence, this study aims to explore roles that HNF4α plays in the CRC development. RNA quantification analysis was conducted to characterize the expression pattern of long intergenic noncoding RNA 00511 (LINC00511)/HNF4α/IL-24 in CRC tissues and cell lines. Using gain- and loss-of-function approaches, effects of HNF4α/LINC00511/IL-24 axis on biological processes such as proliferative, migrating, invading, apoptotic, and tumorigenic functions of CRC cells were evaluated. We further identified the interactions among HNF4α/LINC00511/EZH2/IL-24 using RNA binding protein immunoprecipitation, RNA pull-down along with chromatin immunoprecipitation (ChIP). LINC00511 was an upregulated lncRNA in CRC tissues and cells, which played an oncogenic role by strengthening the malignant phenotypes of CRC cells. LINC00511 downregulated IL-24 expression by interacting with EZH2. HNF4α could enhance LINC00511 transcription in an epigenetic manner, which finally accelerated cancer progression and tumorigenesis through LINC00511-mediated inhibition of IL-24. Those data together demonstrated the contribution of HNF4α to the progression of CRC through mediating the LINC00511/EZH2/IL-24 axis. Hence, our study provides a promising therapeutic target for CRC.NEW & NOTEWORTHY Our findings on the roles of hepatocyte nuclear factor 4 α/long intergenic noncoding RNA 00511/IL-24 axis provide new insights into the CRC and offer potential targets for translational applications.

Expression of microRNA-328 Functions as a Biomarker for Recurrence of Early Gastric Cancer (EGC) After Endoscopic Submucosal Dissection (ESD) by Modulating CD44.

BACKGROUND This study investigated the molecular mechanism of the effect of CD44 on the recurrence of EGC after ESD, including the potential regulator and signaling pathways of CD44. MATERIAL AND METHODS We searched the miRNA online database (www.mirdb.org) with the "seed sequence" located within the 3'-UTR of the target gene, and performed luciferase assay to test the miRNA/mRNA relationship. We also determined the expression of CD44 in the EGC and control samples. In addition, statistical analysis was used to explore the role of miR-328 as a biomarker to predict the recurrence after ECD. RESULTS We validated CD44 to be the direct gene via luciferase reporter assay system. We also established the negative regulatory relationship between miR-328 and CD44 via studying the relative luciferase activity at different concentrations of miR-328 mimics. We also conducted real-time PCR and Western blot analysis to study the mRNA and protein expression level of CD44 among different groups (recurrence-positive and recurrence-negative) or cells treated with different concentrations of miR-328 mimics/inhibitors, indicating the negative regulatory relationship between miR-328 and CD44. We also investigated the relative viability of EGC cells when transfected with miR-328 mimics (50 nM and 100 nM) and miR-328 inhibitors (100 nM) to validate miR-328 to be negatively interfering with the viability of EGC cells. miR-328 was also recognized as a potential biomarker to predict recurrence after ESD in EGC patients via analysis of the recurrence-free rate among different groups of EGC patients. CONCLUSIONS The expression level of miR-328 can function as a predictive biomarker of recurrence after ECD in patients with EGC via targeting CD44.

Comparison between laparoscopic and endoscopic resections for gastric submucosal tumors.

BACKGROUND/AIMS: Open resection/laparoscopic resection (LR) is the traditional treatment of gastric submucosal tumor (G-SMT). The endoscopic resection (ER) technology provides good results for G-SMT treatment but lacks sufficient evidence-based evidence. This retrospective study aimed to compare the clinical efficacy of ER [endoscopic submucosal dissection (ESD), endoscopic submucosal excavation (ESE), and endoscopic full-thickness resection (EFR)] and LR [laparoscopic wedge resection (LWR) and laparoscopic subtotal gastrectomy (LSG)] for G-SMT. PATIENTS AND METHODS: From January 2013 to January 2017, data of patients with G-SMT with tumor diameter <5 cm were collected from the database of The Affiliated Hospital of Qingdao University and classified based on surgical methods. Demographics, tumor characteristics, surgical outcomes, complications and tumor recurrence were recorded and compared. RESULTS: Overall, 275 patients with G-SMT were enrolled: 152 underwent ER (ESD, n = 65; ESE, n = 23; EFR, n = 61) and 123 underwent LR (LWR, n = 93; LSG, n = 30). Age, sex, R0 resection rate, tumor location, type, recurrence and complications were not statistically significant (P > 0.05). The ER group had a significantly higher percentage of intraluminal tumor (94.1% vs 62.4%) and smaller tumor size (1.8 ± 0.8 vs 3.4 ± 1.2 cm) than the LR group. The ER group had less muscular tumors than the LR group (54.6% vs 70.7%). The ER group had no serosal tumor. The ER group had shorter hospitalization time, postoperative hospital stay and diet recovery time. The LR group had shorter operation time, less cost and less blood loss. CONCLUSION: ER and LR are safe and effective treatments for SMT. For small intraluminally growing SMT, ER is better than LR.

The lncRNA ZEB1-AS1 sponges miR-181a-5p to promote colorectal cancer cell proliferation by regulating Wnt/ß-catenin signaling.

Long noncoding RNAs (lncRNAs) are important regulators of the biological functions and underlying molecular mechanisms of colorectal cancer (CRC). However, the role of the lncRNA ZEB1-AS1 in CRC is not thoroughly understood. In this study, we found that ZEB1-AS1 was markedly upregulated in CRC. ZEB1-AS1 knockdown significantly suppressed CRC cell proliferation and induced apoptosis, whereas enhanced expression of ZEB1-AS1 had the opposite effect. Bioinformatics analysis identified miR-181a-5p as a candidate target of ZEB1-AS1. Moreover, we found an inverse correlation between ZEB1-AS1 and miR-181a-5p expression in CRC tissue. Inhibition of miR-181a-5p significantly upregulated ZEB1-AS1, whereas overexpression of miR-181a-5p had the opposite effect, suggesting that ZEB1-AS1 is negatively regulated by miR-181a-5p. Using luciferase reporter and RIP assays, we found that miR-181a-5p directly targets ZEB1-AS1. Importantly, ZEB1-AS1 may act as an endogenous 'sponge' to regulate miRNA targets by competing for miR-181a-5p binding. In summary, our findings provide the evidence supporting the role of ZEB1-AS1 as an oncogene in CRC. Our study also demonstrates that miR-181a-5p targets not only protein-coding genes but also the lncRNA ZEB1-AS1.