Downregulation of Lgr6 inhibits proliferation and invasion and increases apoptosis in human colorectal cancer

Wang, Fei; Dai, Chun‐Qian; Zhang, Lirong; Cao, Bing; Qin, Jun; Liu, Yifei

doi:10.3892/ijmm.2018.3633

Cited by 11 publications

(13 citation statements)

References 38 publications

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“…There are limited epidemiological reports on the association between these markers and CRC risk. One of the genes, LGR6 (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 6) regulates the phosphoinositide 3-kinase/AKT signaling pathway and plays a tumor-promoting role in CRC development indicating that it might be a potential diagnostic and prognostic biomarker for CRC [42]. Protein tyrosine phosphatase non-receptor type 12 (PTPN12) are signaling molecules that regulate a variety of cellular processes and has been found to be epigenetically regulated in triple-negative breast cancer [43].…”

Section: Discussionmentioning

confidence: 99%

A panel of DNA methylation signature from peripheral blood may predict colorectal cancer susceptibility

Onwuka

Liu

et al. 2020

BMC Cancer

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Background: Differential DNA methylation panel derived from peripheral blood could serve as biomarkers of CRC susceptibility. However, most of the previous studies utilized post-diagnostic blood DNA which may be markers of disease rather than susceptibility. In addition, only a few studies have evaluated the predictive potential of differential DNA methylation in CRC in a prospective cohort and on a genome-wide basis. The aim of this study was to identify a potential panel of DNA methylation biomarkers in peripheral blood that is associated with CRC risk and therefore serve as epigenetic biomarkers of disease susceptibility. Methods: DNA methylation profile of a nested case-control study with 166 CRC and 424 healthy normal subjects were obtained from the Gene Expression Omnibus (GEO) database. The differentially methylated markers were identified by moderated t-statistics. The DNA methylation panel was constructed by stepwise logistic regression and the least absolute shrinkage and selection operator in the training dataset. A methylation risk score (MRS) model was constructed and the association between MRS and CRC risk assessed. Results: We identified 48 differentially methylated CpGs sites, of which 33 were hypomethylated. Of these, sixteen-CpG based MRS that was associated with CRC risk (OR = 2.68, 95% CI: 2.13, 3.38, P < 0.0001) was constructed. This association is confirmed in the testing dataset (OR = 2.02, 95% CI: 1.48, 2.74, P < 0.0001) and persisted in both males and females, younger and older subjects, short and long time-to-diagnosis. The MRS also predicted CRC with AUC 0.82 (95% CI: 0.76, 0.88), indicating high accuracy. Conclusions: Our study has identified a novel DNA methylation panel that is associated with CRC and could, if validated be useful for the prediction of CRC risk in the future.

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Section: Discussionmentioning

confidence: 99%

A panel of DNA methylation signature from peripheral blood may predict colorectal cancer susceptibility

Onwuka

Liu

et al. 2020

BMC Cancer

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“…In this study, we modulated Wnt/β-catenin signalling in the HF JZ using LGR6 is a high affinity receptor for R-spondin, which potentiates Wnt signalling, and Lgr6 can induce stemness (e.g. of ovarian cancer cells 45 , colorectal cancer cells 46 ) by enhancing Wnt/β-catenin signalling. This considered, our data here could be taken to suggest that active Wnt signalling may set up autocrine signalling loops that reinforce the stem cell identity in the JZ.…”

Section: Discussionmentioning

confidence: 99%

Aberrant Wnt signalling induces comedo-like changes in the upper hair follicle

Shang¹,

Tan²,

Steensel³

et al. 2020

Preprint

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Comedonal acne is a common skin disease characterized by cystic dilation of the hair follicle junctional zone. While the molecular mechanisms of acne pathogenesis are not well understood, an emerging hypothesis holds that imbalances in key signalling pathways may lead to abnormal fate determination of sebaceous progenitor cells. The subsequent accumulation of cells could then cause cyst formation in the hair follicle junctional zone and lower infundibulum, forming blackheads. This notion is supported by the observation that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes severe comedonic acne and seboatrophy by inducing fate changes in Lrig1-expressing stem cells, as well as recent human GWAS studies implicating the Wnt signalling pathway in acne. To test the possible involvement of Wnt signals in blackhead formation, we used an Lrig1-CreERT2 mouse line to modulate Wnt signalling in stem cells of the junctional zone, which are known to contribute to the junctional zone, infundibulum, and sebaceous glands. We find that persistent activation of Wnt signalling in the junctional zone leads to formation of comedone-like cysts with associated atrophic sebaceous glands. The cysts strongly express stem cell markers and can be partially reduced by treatment with all-trans retinoic acid, a well-established acne treatment, as well as by inhibition of Hedgehog signalling. In contrast, loss of Wnt signalling leads to enlargement of the junctional zone, infundibulum and sebaceous glands. These data lead us to suggest that abnormal Wnt signalling could be involved in acne pathogenesis by inhibiting differentiation and retaining junctional zone cells in a proliferative progenitor state, leading to their accumulation into comedones.

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“…LGR6 is reported to promote cancer development and, when suppressed, induces apoptosis 25 . Moreover, the protein encoded by LGR6 has been specifically detected on the surface of progenitor cells that likely give rise to luminal-type mammary tumors 26 .…”

Section: Discussionmentioning

confidence: 99%

High-throughput allelic expression imbalance analyses identify candidate breast cancer risk genes

Marjaneh

Sivakumaran

Hillman

et al. 2019

Preprint

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Fine-mapping of breast cancer GWAS regions has identified 195 high confidence signals containing more than 5,000 credible causal variants (CCVs). The CCVs are predominantly noncoding and enriched in regulatory elements and thus may confer the risk by altering gene expression in cis. We analyzed allelic expression imbalance (AEI) of genes surrounding known breast cancer signals, using normal breast and breast tumor transcriptome data and imputed genotypes. Fourteen genes, including NTN4, were identified whose expression was associated with CCV genotype. We showed that CCVs at this signal were located within an enhancer that physically interacts with the NTN4 promoter. Furthermore, knockdown of NTN4 in breast cells increased cell proliferation in vitro and tumor growth in vivo. Here, we present the most comprehensive AEI analysis of breast cancer CCVs resulting in identification of new candidate risk genes.

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Downregulation of Lgr6 inhibits proliferation and invasion and increases apoptosis in human colorectal cancer

Cited by 11 publications

References 38 publications

A panel of DNA methylation signature from peripheral blood may predict colorectal cancer susceptibility

A panel of DNA methylation signature from peripheral blood may predict colorectal cancer susceptibility

Aberrant Wnt signalling induces comedo-like changes in the upper hair follicle

High-throughput allelic expression imbalance analyses identify candidate breast cancer risk genes

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