Novel DNA methylation markers with potential prognostic relevance in advanced malignant melanoma identified using COBRA assays

Kaehler, Katharina C.; Politz, Oliver; Henderson, David; Ulbrich, Hannes-Friedrich; Hauschild, Axel; Mund, Cora; Egberts, Friederike

doi:10.1097/cmr.0000000000000150

Cited by 8 publications

(6 citation statements)

References 20 publications

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“…BASP1 expression is found to be downregulated in several cancers including hepatocellular carcinoma, prostate cancer, and melanoma. [ 20 21 22 ] In the present study, we also found BASP1 expression was downregulated in thyroid cancer tissues and this downregulation was correlated with poorer prognosis, which indicated BASP1 acted as tumor suppressor in thyroid cancer. Neither BASP1 mRNA nor protein was detected in BHT101 and KMH-2 cells, indicating that the absence of BASP1 expression may be attributed to pretranscriptional deregulation.…”

Section: Discussionsupporting

confidence: 65%

Restoration of Brain Acid Soluble Protein 1 Inhibits Proliferation and Migration of Thyroid Cancer Cells

Guo

Chen

et al. 2016

Chinese Medical Journal

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Background:Brain acid soluble protein 1 (BASP1) is identified as a novel potential tumor suppressor in several cancers. However, its role in thyroid cancer has not been investigated yet. In the present study, the antitumor activities of BASP1 against the growth and migration of thyroid cancer cells were evaluated.Methods:BASP1 expression in thyroid cancer tissues and normal tissues were examined by immunohistochemical staining and the association between its expression and prognosis was analyzed. pcDNA-BASP1 carrying full length of BASP1 cDNA was constructed to restore the expression of BASP1 in thyroid cancer cell lines (BHT-101 and KMH-2). The cell proliferation in vitro and in vivo was evaluated by WST-1 assay and xenograft tumor models, respectively. Cell cycle distribution after transfection was analyzed using flow cytometry. Cell apoptosis after transfection was examined by annexin V/propidium iodide assay. The migration was examined using transwell assay.Results:BASP1 expression was abundant in normal tissues while it is significantly decreased in cancer tissues (P = 0.000). pcDNA-BASP1 restored the expression of BASP1 and significantly inhibited the growth of BHT-101 and KMH-2 cells as well as xenograft tumors in nude mice (P = 0.000). pcDNA-BASP1 induced G1 arrest and apoptosis in BHT-101 and KMH-2 cells. In addition, pcDNA-BASP1 significantly inhibited the cell migration.Conclusions:Downregulation of BASP1 expression may play a role in the tumorigenesis of thyroid cancer. Restoration of BASP1 expression exerted extensive antitumor activities against growth and migration of thyroid cancer cells, which suggested that BASP1 gene might act as a potential therapeutic agent for the treatment of thyroid cancer.

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Section: Discussionsupporting

confidence: 65%

Restoration of Brain Acid Soluble Protein 1 Inhibits Proliferation and Migration of Thyroid Cancer Cells

Guo

Chen

et al. 2016

Chinese Medical Journal

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“…This corroborates our original finding that BASP1 strongly interferes with v‐Myc‐induced oncogenicity and displays properties of a tumor suppressor (Hartl et al , ). In multiple carcinoma, melanoma, and leukemia cells, BASP1 transcription is silenced by promoter methylation (Kaehler et al , ; Moribe et al , ; Zhou et al , ), a typical DNA modification in the regulatory regions of tumor suppressors in cancer. An important function of BASP1 is to act as a transcriptional cosuppressor of the Wilms’ tumor suppressor protein WT1, converting the WT1 oncoprotein into a tumor suppressor (Carpenter et al , ; Goodfellow et al , ; Toska et al , ; Toska et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…Strong support for the proposal that BASP1 acts as a potential tumor suppressor came from recent observations in human and animal cancer. BASP1 is downregulated in several mammalian tumors including carcinoma, acute and chronic lymphocytic leukemia, and melanoma (Kaehler et al , ; Moribe et al , ; Ransohoff et al , ; Tchernitsa et al , ; Wang et al , ; Xu et al , ; Yeoh et al , ). BASP1 is also downregulated in lung cancer by specific miR‐191‐mediated mRNA degradation (Xu et al , ).…”

Section: Introductionmentioning

confidence: 99%

The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

et al. 2020

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The MYC protein is a transcription factor with oncogenic potential controlling fundamental cellular processes such as cell proliferation, metabolism, differentiation, and apoptosis. The MYC gene is a major cancer driver, and elevated MYC protein levels are a hallmark of most human cancers. We have previously shown that the brain acid‐soluble protein 1 gene (BASP1) is specifically downregulated by the v‐myc oncogene and that ectopic BASP1 expression inhibits v‐myc‐induced cell transformation. The 11‐amino acid effector domain of the BASP1 protein interacts with the calcium sensor calmodulin (CaM) and is mainly responsible for this inhibitory function. We also reported recently that CaM interacts with all MYC variant proteins and that ectopic CaM increases the transactivation and transformation potential of the v‐Myc protein. Here, we show that the presence of excess BASP1 or of a synthetic BASP1 effector domain peptide leads to displacement of v‐Myc from CaM. The protein stability of v‐Myc is decreased in cells co‐expressing v‐Myc and BASP1, which may account for the inhibition of v‐Myc. Furthermore, suppression of v‐Myc‐triggered transcriptional activation and cell transformation is compensated by ectopic CaM, suggesting that BASP1‐mediated withdrawal of CaM from v‐Myc is a crucial event in the inhibition. In view of the tumor‐suppressive role of BASP1 which was recently also reported for human cancer, small compounds or peptides based on the BASP1 effector domain could be used in drug development strategies aimed at tumors with high MYC expression.

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“…The role of BASP1 protein in cancer has not been well established. One study demonstrated an association between increased BASP1 expression in stage III and stage IV melanoma tumor cells and improved melanoma survival [10]. Consistent with a protective role for BASP1 in melanoma, we found that BASP1 expression was suppressed in melanoma ( N = 45) as compared with benign nevi ( N = 18) by 0.26 fold ( P = 0.007, moderated t-statistic) using publicly available expression data (GEO, GDS1375/GSE3189) (Figure 2) [11, 12].…”

Section: Discussionmentioning

confidence: 99%

Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma

Ransohoff

Cho

et al. 2017

Oncotarget

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Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M.D. Anderson Cancer Center. We performed a combined meta-analysis totaling 6,628 melanoma cases and 287,591 controls. Our study replicates 20 of 21 previously known melanoma-loci and confirms the association of the telomerase reverse transcriptase, TERT, with melanoma susceptibility at genome-wide significance. In addition, we uncover a novel polymorphism, rs187843643 (OR = 1.96; 95% CI = [1.54, 2.48]; P = 3.53 × 10−8), associated with melanoma. The SNP rs187842643 lies within a noncoding RNA 177kb downstream of BASP1 (brain associated protein-1). We find that BASP1 expression is suppressed in melanoma as compared with benign nevi, providing additional evidence for a putative role in melanoma pathogenesis.

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Novel DNA methylation markers with potential prognostic relevance in advanced malignant melanoma identified using COBRA assays

Cited by 8 publications

References 20 publications

Restoration of Brain Acid Soluble Protein 1 Inhibits Proliferation and Migration of Thyroid Cancer Cells

Restoration of Brain Acid Soluble Protein 1 Inhibits Proliferation and Migration of Thyroid Cancer Cells

The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma

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