Stage-specific methylome screen identifies that NEFL is downregulated by promoter hypermethylation in breast cancer

Kang, Seongeun; Kim, Byungtak; Park, Sung-Bin; Jeong, Gookjoo; Kang, Hyejin; Liu, Ran; Kim, Sun Jung

doi:10.3892/ijo.2013.2094

Cited by 15 publications

(12 citation statements)

References 29 publications

(31 reference statements)

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“…Sebastien Jauliac found that NFAT5 were expressed in invasive human ductal breast carcinomas and participate in promoting carcinoma invasion using cell lines derived from human breast and colon carcinomas [31]. NEFL has been shown to act as a tumor suppressor in the carcinogenesis of breast [32], [33]. However, we found significant association between these three SNPs and breast cancer risk only in stage I.…”

Section: Discussioncontrasting

confidence: 49%

miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk

Zheng

et al. 2014

PLoS ONE

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BackgroundSingle nucleotide polymorphisms (SNPs) that reside in microRNA target sites may play an important role in breast cancer development and progression. To reveal the association between microRNA target site SNPs and breast cancer risk, we performed a large case-control study in China.MethodsWe performed a two-stage case-control study including 2744 breast cancer cases and 3125 controls. In Stage I, we genotyped 192 SNPs within microRNA binding sites identified from the “Patrocles” database using custom Illumina GoldenGate VeraCode assays on the Illumina BeadXpress platform. In Stage II, genotyping was performed on SNPs potentially associated with breast cancer risk using the TaqMan platform in an independent replication set.ResultsIn stage I, 15 SNPs were identified to be significantly associated with breast cancer risk (P<0.05). In stage II, one SNP rs8752 was replicated at P<0.05. This SNP is located in the 3’ untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene at 4q34-35, a miR-485-5p binding site. Compared with the GG genotype, the combined GA+AA genotypes has a significantly higher risk of breast cancer (OR = 1.18; 95% CI: 1.06-1.31, P = 0.002). Specifically, this SNP was associated with estrogen receptor (ER) positive breast cancer (P = 0.0007), but not with ER negative breast cancer (P = 0.23), though p for heterogeneity not significant.ConclusionThrough a systematic case-control study of microRNA binding site SNPs, we identified a new breast cancer risk variant rs8752 in HPGD in Chinese women. Further studies are warranted to investigate the underling mechanism for this association.

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Section: Discussioncontrasting

confidence: 49%

miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk

Zheng

et al. 2014

PLoS ONE

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“…32 Also, abnormal genespecific promoter hypermethylation is closely associated with the occurrence and development of breast cancer. 33 The absence of Cosmc contributes to the expression of the Tn antigen through the regulation of T-synthase, which is related to the development and progression of various human diseases, including cancer. 34,35 For instance, a recent study has found that Cosmc deficient pancreatic cancer cell line Tn STn Promote breast cancer progression Figure 5 The molecular mechanism involving the regulatory roles of Cosmc/Tn/STn in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens</p>

Wang

Cui

et al. 2020

CMAR

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These authors contributed equally to this workBackground: Aberrant gene methylation in breast cancer is associated with an unfavorable prognosis. Besides, abnormal Cosmc can induce the expression of Tn and STn antigens. The present study aimed to investigate the roles of Cosmc promoter methylation in breast cancer through the regulation of Tn and STn antigens. Methods: The expression patterns of Cosmc and the Tn and STn antigens in breast cancer cell lines were determined. Cosmc was overexpressed to explore the effects of Cosmc on cell behavior, including the growth, migration, invasion, and apoptosis of breast cancer cells and tumor growth with in vitro and in vivo experiments. Afterwards, a methyltransferase and a methyltransferase inhibitor were used to alter the methylation status of Cosmc to explore the mechanisms related to Cosmc promoter methylation. Results: Cosmc was poorly expressed in breast cancer cells. Cosmc overexpression inhibited cell growth, migration, and invasion while promoting apoptosis in breast cancer cells in vitro and restraining tumor growth in vivo. Cosmc promoter methylation was found to decrease the levels of Cosmc and increased the expression of the Tn and STn antigens in breast cancer. Conclusion: In conclusion, the demethylation of Cosmc mitigates breast cancer progression through the repression of the Tn and STn antigens, which provides evidence for therapeutic considerations for a novel target against breast cancer.

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“…siR-NEFL group. *p \ 0.05, **p \ 0.01, ***p \ 0.001, #p \ 0.05, ##p \ 0.01, ###p \ 0.001 heterozygous and homozygous deletions in a variety of common human cancers, including prostate cancer [30], breast cancer [31,32], and head and neck cancer (HNC) [27,33]. NEFL, a potential tumor suppresser [30,31,33], is associated with resistance to chemosensitivity.…”

Section: Discussionmentioning

confidence: 99%

miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL

Peng

Yuan

et al. 2015

Mol Cell Biochem

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Glioblastoma multiforme (GBM) is the most malignant and common brain tumor; it is aggressive growth pattern means that GBM patients face a poor prognosis even when receiving the best available treatment modalities. In recent years, an increasing number of reports suggest that the discovery of microRNAs (miRNAs) might provide a novel therapeutic target for human cancers, including GBM. One miRNA in particular, microRNA-25 (miR-25), is overexpressed in several cancers, wherein accumulating evidence indicates that it functions as an oncogene. However, the function of miR-25 in GBM has not been totally elucidated. In this study, we demonstrated that miR-25 was significantly up-regulated in astrocytoma tissues and glioblastoma cell lines. In vitro studies further demonstrated that overexpressed miR-25 was able to promote, while its antisense oligos inhibited cell proliferation and invasion in U251 cells. Moreover, we identified neurofilament light polypeptide (NEFL) as a novel target molecule of miR-25. Also of note was the fact that NEFL was down-regulated with increased levels of miR-25 expression in human astrocytoma clinical specimens. In addition, via the mTOR signaling pathway, NEFL-siRNA could significantly attenuate the inhibitory effects of knockdown miR-25 on the proliferation and invasion of U251 cells. Overall, our results showed an important role for miR-25 in regulating NEFL expression in GBM, and suggest that miR-25 could be a potential target for GBM treatment.

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Stage-specific methylome screen identifies that NEFL is downregulated by promoter hypermethylation in breast cancer

Cited by 15 publications

References 29 publications

miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk

miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk

<p>Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens</p>

miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL

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