Erratum: Linc-KILH potentiates Notch1 signaling through inhibiting KRT19 phosphorylation and promotes the malignancy of hepatocellular carcinoma: Erratum.

[This corrects the article DOI: 10.7150/ijbs.52279.].

m6A demethylase ALKBH5 maintains stemness of intrahepatic cholangiocarcinoma by sustaining BUB1B expression and cell proliferation.

ALKBH5 plays critical roles in various cellular processes via post-transcriptional regulation of oncogenes or tumor suppressors in an N6-methyladenosine (m6A)-dependent manner. However, its function in intrahepatic cholangiocarcinoma (ICC) remains unclear. In the present study, bioinformatic analyses of The Cancer Genome Atlas (TCGA) data were performed, and the association of ALKBH5 in predicting overall survival in patients with ICC was investigated. Then, the clinical data of patients from The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University (Changzhou, China) was used to reveal the overall survival of patients with ICC with different ALKBH5 expression levels by Kaplan-Meier survival analysis. Subsequently, in vitro and in vivo studies were conducted to explore and verify the downstream genes regulated by ALKBH5. The results from TCGA data demonstrated that ALKBH5 expression is elevated in ICC and that patients with high ALKBH5 expression exhibited poor survival compared with patients with low expression. In addition, in vitro assays demonstrated that ALKBH5 promoted cell viability and maintained the stemness of ICC cells, leading to ICC progression. The present study also demonstrated that BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is the downstream gene regulated by ALKBH5 and targeting BUB1B suppressed cell growth. The in vitro and vivo experiments revealed that ALKBH5 might function through BUB1B to maintain the stemness of ICC and that altering BUB1B may suppress ICC progression.

LncRNA GSTM3TV2 Promotes Cell Proliferation and Invasion via miR-597/FOSL2 Axis in Hepatocellular Carcinoma.

Mounting evidence has recently shown that role of long noncoding RNA is critical in many human cancers. lncRNA GSTM3TV2 was first proven to play a vital role in pancreatic cancer. However, the mechanism of lncRNA GSTM3TV2 in hepatocellular carcinoma (HCC) is still uncovered. Here, we object to distinguish the expression of lncRNA GSTM3TV2 and reveal its mechanistic relationship with HCC. We observed that the expression of lncRNA GSTM3TV2 and FOSL2 were upregulated in HCC. Knockdown of lncRNA GSTM3TV2 significantly inhibited cell proliferation. Meanwhile, the migration and invasion of HCC cells were greatly decreased by the downregulated lncRNA GSTM3TV2. The luciferase reporter assays showed that lncRNA GSTM3TV2 could be directly bound to miR-597, and the level of miR-597 was also decreased in the tumor tissues. lncRNA GSTM3TV2 could stabilize FOSL2 expression, resulting in the oncogenic properties of lncRNA GSTM3TV2 in HCC. Our study indicated the oncogenic activities of lncRNA GSTM3TV2 and emphasized the role of the miR-597/FOSL2 signaling pathway.

Linc-KILH potentiates Notch1 signaling through inhibiting KRT19 phosphorylation and promotes the malignancy of hepatocellular carcinoma.

Long noncoding RNAs (LncRNAs) are emerging as crucial regulators in the pathophysiological process of various tumors, including HCC. Here, we identify a novel lncRNA Linc-KILH (KRT19 interacting long noncoding RNA in hepatocellular carcinoma), which is significantly up-regulated in HCC tissues and positively correlated with larger tumor size, severer microvascular invasion, more intrahepatic metastasis and decreased survival of HCC patients. Silence of Linc-KILH remarkably inhibited the proliferation and metastasis abilities of KRT19-positive HCC cells in vitro and in vivo. Mechanistically, Linc-KILH interacts with KRT19 and then inhibits the phosphorylation of KRT19 on Ser35, thereby, enhancing the translocation of KRT19 from cytoplasm to membrane in KRT19 positive HCC cells. Additionally, we validated that KRT19 interacts with ß-catenin but not RAC1 in HCC cells. Linc-KILH enhanced the interaction between ß-catenin and KRT19 in cytoplasm and promoted the nuclear translocation of ß-catenin in HCC cells. Furthermore, Linc-KILH could enhance the promoting function of KRT19 on Notch1 signaling with the existence of KRT19 in HCC cells. Collectively, we revealed that Linc-KILH exerts a vital function in KRT19 positive HCC progression and may likely be developed into an effective therapeutic target for HCC.

ARRB1 Drives Gallbladder Cancer Progression by Facilitating TAK1/MAPK Signaling Activation.

Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract, with a dismal 5-year survival of 5%. Recently, ARRB1, as a molecular scaffold, has been proposed to participate in the progression of multiple malignancies. However, the effect and regulatory mechanisms of ARRB1 in GBC have not been investigated. Our study aimed to explore the biological functional status and the possible molecular mechanisms of ARRB1 with respect to GBC progression. The survey showed that human GBC tissues exhibited increased levels of ARRB1 compared with normal tissues, and the high expression of ARRB1 was associated with poor prognosis of GBC patients. A series of in vitro and in vivo functional experiments based on knockdown of ARRB1 uncovered that ARRB1 enhanced GBC cell proliferation, migration, and invasion. Furthermore, we reported that TAK1, a component of the TNF /MAPK pathway, is a vital downstream effector of ARRB1. In addition, siTAK1 could abolish the functional changes between ARRB1 overexpression GBC cells and control ones. Our data revealed that ARRB1 facilitated the carcinogenesis and development of GBC through TNF/TAK1/MAPK axis, suggesting that ARRB1 may be a promising biomarker and treatment target for GBC patients.

Relationship Between Tumor Necrosis Factor-α rs361525 Polymorphism and Gastric Cancer Risk: A Meta-Analysis.

Tumor necrosis factor (TNF)-α, a major part in inflammatory, infectious and tumor processes, and is pivotal at the early stages of gastric cancer. Relationship between its risk and TNF-α rs361525 polymorphism has been demonstrated, but remains conflicting and controversial. Therefore, a meta-analysis was conducted to more precisely estimate this relationship. PubMed, Web of Science, EMBASE and CNKI were comprehensively searched to find out relevant articles through October 5, 2017. The strength of the relationship was assessed using pooled odds ratios and 95% confidence intervals. Totally 20 articles were included involving 4,084 cases and 7,010 controls. No significant relationship between TNF-α rs361525 polymorphism and increased GC risk was found in the whole populations. Subgroup analyses uncovered TNF-α rs361525 polymorphism intensified the risk of GC among Asians under five models, but decreased the risk of GC among Caucasiansin the allelic and dominant models. Subgroup analysis by genotyping methods revealed increased risk for other methods. In conclusion, this meta-analysis suggests TNF-α rs361525 polymorphism is related to the risk of GC, especially for Asians.

MYO9B gene polymorphisms are associated with the risk of inflammatory bowel diseases.

Myosin IXB (MYO9B) gene polymorphisms have been extensively investigated in terms of their associations with inflammatory bowel disease (IBD), with contradictory results. The aim of this meta-analysis was to evaluate associations between MY09B gene polymorphisms and the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Eligible studies from PubMed, Embase, and CNKI databases were identified. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Ten studies published in eight papers reporting 8,975 cases and 9,482 controls were included in this meta-analysis. Five MY09B gene polymorphisms were evaluated: rs1545620, rs962917, rs1457092, rs2305764, and rs2305767. Our data suggested that the rs1545620 polymorphism was associated with a decreased risk of IBD. A similar result was found for rs2305767 and UC. The rs962917 single nucleotide polymorphism (SNP) increased the risk of IBD, CD and UC. Moreover, rs1457092 increased the risk of IBD and UC. Rs2305764 was also associated with an increased risk of IBD. Furthermore, stratification analyses indicated that rs1545620 decreased the risk of IBD, while rs962917 increased the risk of IBD, CD and UC in Caucasian populations. To sum up, our data indicate that these five SNPs in MY09B are significantly associated with the risk of IBD.

Relationship between LRRK2 R1628P polymorphism and Parkinson's disease in Asian populations.

Although the leucine-rich repeat kinase 2 (LRRK2) R1628P polymorphism has been associated with the risk of Parkinson's disease (PD) in Taiwan, China, and Singapore, there are conflicting findings regarding this relationship. Thus, the aim of the present meta-analysis was to evaluate the associations between the LRRK2 R1628P polymorphism (rs33949390) and PD in Asian populations. A search for eligible studies was performed in PubMed, Embase, SinoMed, and the China Knowledge Resource Integrated Database, and pooled odds ratios and 95% confidence intervals were used to evaluate the strength of the association between the R1628P polymorphism and PD. This meta-analysis assessed 19 studies from 14 papers that involved a total of 9,927 PD patients and 8,602 controls and found that the R1628P polymorphism was significantly associated with the risk of PD in Asian populations. Moreover, stratification analyses indicated that the R1628P polymorphism was significantly associated with an increased risk of PD among Chinese as well as non-Chinese Asian populations and an increased risk of PD in Chinese patients from China, Taiwan, and Singapore. In a stratified analysis conducted according to age, significant associations were found for both late-onset PD and early-onset PD. The present data indicate that the R1628P polymorphism of the LRRK2 gene contributes to PD susceptibility in Asian, especially Chinese, populations.

Re: "PICALM Gene rs3851179 Polymorphism Contributes to Alzheimer's Disease in an Asian Population".

Liu et al. have carried out a meta-analysis of case-control studies to investigate the association between PICALM gene rs3851179 polymorphism and Alzheimer's disease in an Asian population. However, several important issues should be noted.