Epigenetically controlled Six3 expression regulates glioblastoma cell proliferation and invasion alongside modulating the activation levels of WNT pathway members

Feng

Clinical Laboratory Analysis

et al. 2019

BackgroundIt has indicated that single nuclear polymorphisms (SNPs) in the regions encoding non‐coding transcripts are associated with lung cancer susceptibility. In a previous microarray study, we identified 13 differentially expressed long non‐coding RNAs (lncRNAs) in non‐small cell lung cancer (NSCLC) and associations of SNPs in these lncRNA genes with lung cancer were unknown. We conducted a case‐control study to address this issue.MethodsUsing the TaqMan method, we genotyped 17 SNPs located in the 13 lncRNA genes in 1294 cases with NSCLC and 1729 healthy controls. Unconditional logistic regression and Cox proportional hazards regression were used to analyze the associations of these SNPs with NSCLC risk and patient survival, respectively. These analyses were also repeated in subgroups of cases and controls stratified by gender, age group, smoking status, disease stage, and histological type.ResultsWe identified three SNPs associated with NSCLC risk. For SNP rs498238, CC genotype was associated with lower risk compared to TT genotype (adjusted OR = 0.33, 95%CI: 0.11‐0.97, P = 0.043). For rs16901995, CT/TT genotypes were associated with lower risk compared to CC genotype in non‐smokers (adjusted OR = 0.78, 95%CI: 0.62‐0.98, P = 0.035). Variant genotypes in rs219741 were associated with NSCLC risk in young patients, and the adjusted OR was 1.47 (95%CI: 1.03‐2.10, P = 0.033) when compared to the wild genotype. No SNPs were found to be associated with patient overall survival in the study.ConclusionThe study suggests that some genetic polymorphisms in the lncRNA genes may influence the risk of NSCLC among Chinese.

Section: Discussionsupporting

confidence: 60%

SNPs in LncRNA genes are associated with non‐small cell lung cancer in a Chinese population

Feng

Clinical Laboratory Analysis

et al. 2019

Journal Cellular Physiology

“…Likewisely, loss of Six3 is involved in the initiation and progression of human glioma via increasing Wnt/β-catenin signaling (B. Zhang, Shen, Ge, Ma, & Zhang, 2017). However, dapper homolog 2 (DACT2) acts as a tumor suppressor to suppress growth and induce apoptosis of glioma cells by inducing Wnt/β-catenin pathway (Y.…”

Section: Suppressive Roles Of Wnt/ β-Catenin Pathway In Glioma Devementioning

confidence: 99%

Wnt/β‐catenin signaling cascade: A promising target for glioma therapy

Zhou

Zeng

et al. 2018

Glioma is one of the most treatment‐refractory intracranial tumors, and the aberrant expressed Wnt/β‐catenin pathway is closely associated with glioma malignancy. In this regard, Wnt/β‐catenin signaling has been reported to play an essential role in cellular proliferation, migration, invasion, and angiogenesis, therefore contributing to glioma progression. However, the underlying mechanisms of Wnt/β‐catenin signaling involvement in gliomagenesis remain unknown. Here, we present an overview of the Wnt components and then go on to summarize the current knowledge describing the multitude of roles of Wnt/β‐catenin in glioma, which are mediated by transcription factors, microRNAs, long noncoding RNAs, and so on. In the latter portion of the review, we elaborate the increasing apparent crosstalk of Wnt/β‐catenin pathway with PI3K/AKT signaling involved in these processes. Ultimately, compounds targeting the Wnt/β‐catenin are described in glioma. As better understanding of the regulatory mechanisms to glioma malignancies increases, Wnt/β‐catenin cascade may represent an area of developmental glioma therapeutics focus.

“…β-catenin, known as a core component of this signaling, has been determined to be a pivotal contributing factor in a wide range of cancers, including GBM; besides, silencing of β-catenin decreased the expression of c-Myc and Cyclin D1 in GBM cells ( Liu et al., 2011 ). It has been documented that Cyclin D1 and c-Myc were involved in regulation of proliferation in GBM ( Cobanoglu et al., 2016 ; Zhang et al., 2017 ). Consistent with this, indeed, we found that nuclear β-catenin, c-Myc, and Cyclin D1 were inhibited by depletion of CLEC18B.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CLEC18B Associates With the Proliferation, Migration, and Prognosis of Glioblastoma

Guo

Zhao

et al. 2018

ASN Neuro

C-type lectin domain family 18 member B (CLEC18B), encoding a superfamily of CLEC, has been found to be expressed in some of cancer cells, which possibly indicates it associated with cancer. However, the defined functional characterizations of CLEC18B in glioblastoma multiforme (GBM) progression still remain unclear. To this end, clinical relevance of CLEC18B expression with GBM patients’ prognosis was analyzed both in The Cancer Genome Atlas dataset of 174 tissues and 40 GBM tumor tissues collected from our hospital by using the Kaplan–Meier survival and the Cox proportional hazard model. The role of CLEC18B in GBM was determined by loss-of-function assay using small interfering RNA approach in vitro. Functional and signaling analyses were also performed to understand how CLEC18B facilitated the aggressiveness of GBM at molecular and cellular levels using Cell Counting Kit-8 assay, wound-healing, transwell, and Western blot analyses. Results from our analyses showed that CLEC18B was markedly elevated in both GBM tissues and cells, and exhibited strong inverse correlation with overall survival in GBM patients. Moreover, CLEC18B was identified as an independent predictor of patient survival. Functionally, knockdown of CLEC18B inhibited the growth, migration, and invasion of GBM cells. Mechanistic studies revealed that silencing of CLEC18B resulted in downregulation of Wnt/β-catenin signaling activity. Collectively, our findings provide clinical, molecular, and cellular evidence of CLEC18B as a promising prognostic biomarker and therapeutic target for GBM.