Distinct expression patterns of hedgehog ligands between cultured and primary colorectal cancers are associated with aberrant methylation of their promoters

Background: Many microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression patterns have been suggested to correlate with chemo-resistance of cancer cells. We aim to study the role of miR-30 family members in cisplatin-resistance of ovarian cancer cells. Methods: qRT-PCR was used to compare differential expression levels of miR-30 family members in ovarian cancer cell line A2780 and its cisplatin-resistant derivative CP70. Changes of cisplatin-sensitivity in miR-30a-5p- and miR-30c-5p-overexpressed-CP70 cells and miR-30a-5p- and miR-30c-5p-inhibited-A2780 cells were examined by CCK8 assay and apoptosis analysis using flow cytometry; targets of miR-30a/c-5p were analyzed by western blotting and luciferase reporter assay; methylation regulation of pre-miR-30a/c-5p was examined by methylation specific PCR. Results: miR-30a-5p and miR-30c-5p, in contrast to other miR-30 family members, dramatically decreased in cisplatin-resistant CP70 cells due to overexpressed-DNMT1 induced aberrant methylation. miR-30a/c-5p in turn directly inhibited DNMT1 as well as Snail. Forced expression of miR-30a/c-5p or knocking down of DNMT1 and Snail promoted cisplatin susceptibility and partially reversed epithelial-mesenchymal transition (EMT) in CP70 cells, while inhibition of miR-30a/c-5p or ectopic expression of DNMT1 and Snail induced cisplatin resistance and partial EMT in cisplatin-sensitive A2780 cells. Conclusions: A feedback loop between miR-30a/c-5p and DNMT1 is a potent signature for cisplatin-resistance and EMT in ovarian cancer, promising a potential target for improved anti-cancer treatment.

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Gene Expression Patterns in Mismatch Repair-Deficient Colorectal Cancers Highlight the Potential Therapeutic Role of Inhibitors of the Phosphatidylinositol 3-Kinase-AKT-Mammalian Target of Rapamycin Pathway

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-08-2432 ◽

2009 ◽

Vol 15 (8) ◽

pp. 2829-2839 ◽

Cited By ~ 11

Author(s):

Eduardo Vilar ◽

Bhramar Mukherjee ◽

Rork Kuick ◽

Leon Raskin ◽

David E. Misek ◽

...

Keyword(s):

Gene Expression ◽

Mismatch Repair ◽

Expression Patterns ◽

Mammalian Target Of Rapamycin ◽

Colorectal Cancers ◽

Gene Expression Patterns ◽

Phosphatidylinositol 3 Kinase ◽

Therapeutic Role ◽

Potential Therapeutic Role

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Differences in T cell immune-related lncRNA and mRNA expression patterns between right- and left-sided colorectal cancers

Human Immunology ◽

10.1016/j.humimm.2021.08.008 ◽

2021 ◽

Author(s):

Yin Lijuan ◽

Wu Yinhang ◽

Wang Yangyanqiu ◽

Hou Xiaohui ◽

Wei Yunhai ◽

...

Keyword(s):

T Cell ◽

Mrna Expression ◽

Expression Patterns ◽

Colorectal Cancers

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Aberrant Methylation of HLTF, SOCS-1, and CDH13 Genes Is Shown in Colorectal Cancers Without Lymph Node Metastasis

Diseases of the Colon & Rectum ◽

10.1007/s10350-004-0947-7 ◽

2005 ◽

Vol 48 (6) ◽

pp. 1282-1286 ◽

Cited By ~ 11

Author(s):

Kenji Hibi ◽

Yasuhiro Kodera ◽

Katsuki Ito ◽

Seiji Akiyama ◽

Akimasa Nakao

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Colorectal Cancers ◽

Aberrant Methylation ◽

Node Metastasis

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Dynamic patterns of DNA methylation in the normal prostate epithelial differentiation program are targets of aberrant methylation in prostate cancer

Scientific Reports ◽

10.1038/s41598-021-91037-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mark D. Long ◽

Vineet K. Dhiman ◽

Hayley C. Affronti ◽

Qiang Hu ◽

Song Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Methylation ◽

Cell Differentiation ◽

Expression Patterns ◽

Luminal Cell ◽

Multiple Time ◽

Aberrant Methylation ◽

Normal Prostate ◽

Dynamic Patterns ◽

Methylation Patterns

AbstractUnderstanding the epigenetic control of normal differentiation programs might yield principal information about critical regulatory states that are disturbed in cancer. We utilized the established non-malignant HPr1-AR prostate epithelial cell model that upon androgen exposure commits to a luminal cell differentiation trajectory from that of a basal-like state. We profile the dynamic transcriptome associated with this transition at multiple time points (0 h, 1 h, 24 h, 96 h), and confirm that expression patterns are strongly indicative of a progressive basal to luminal cell differentiation program based on human expression signatures. Furthermore, we establish dynamic patterns of DNA methylation associated with this program by use of whole genome bisulfite sequencing (WGBS). Expression patterns associated with androgen induced luminal cell differentiation were found to have significantly elevated DNA methylation dynamics. Shifts in methylation profiles were strongly associated with Polycomb repressed regions and to promoters associated with bivalency, and strongly enriched for binding motifs of AR and MYC. Importantly, we found that dynamic DNA methylation patterns observed in the normal luminal cell differentiation program were significant targets of aberrant methylation in prostate cancer. These findings suggest that the normal dynamics of DNA methylation in luminal differentiation contribute to the aberrant methylation patterns in prostate cancer.

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APC and β-catenin protein expression patterns in HNPCC-related endometrial and colorectal cancers

Familial Cancer ◽

10.1007/s10689-004-6130-4 ◽

2005 ◽

Vol 4 (2) ◽

pp. 187-190 ◽

Cited By ~ 12

Author(s):

Reetta Kariola ◽

Wael M. Abdel-Rahman ◽

Miina Ollikainen ◽

Ralf Butzow ◽

Päivi Peltomäki ◽

...

Keyword(s):

Protein Expression ◽

Expression Patterns ◽

Colorectal Cancers

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A Comprehensive Study of Microsatellite Instability Testing And Its Comparison With Immunohistochemistry In Gastric And Colorectal Cancers

10.21203/rs.3.rs-817395/v1 ◽

2021 ◽

Author(s):

Yujun Park ◽

Soo Kyung Nam ◽

Soo Hyun Seo ◽

Kyoung Un Park ◽

Sang-Hoon Ahn ◽

...

Keyword(s):

Colorectal Cancer ◽

Gastric Cancer ◽

Microsatellite Instability ◽

Expression Patterns ◽

Routine Clinical Practice ◽

Colorectal Cancers ◽

Normal Tissues ◽

Low Incidence ◽

Mmr Proteins ◽

Comprehensive Study

Abstract Background Microsatellite instability (MSI) testing was comprehensively analyzed and compared with immunohistochemistry (IHC) for the mismatch repair (MMR) protein in gastric cancer (GC) and colorectal cancer (CRC). Methods PCR-based MSI testing was performed to compare the tumor and non-neoplastic normal tissues using five microsatellites consisting of two mononucleotide (BAT-26, BAT-25) and three dinucleotide (D5S346, D2S123, and D17S250) in 5,676 GC and 2,553 CRC cases. IHC for the MMR protein MLH1 was done in GCs, and IHC for four MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed in CRCs. Reviews were carried out for discordant or indeterminate IHC cases (such as focal loss of expression, equivocal expression, or abnormal expression patterns). Results MSI-high (MSI-H) and MMR-deficient (dMMR) expression was observed in 521 (9.2%) GC and 171 (6.7%) CRC cases. Discordance between MSI testing and IHC as well as indeterminate IHC cases accounted for 54 (0.9%) and 29 (1.1%) cases out of all GC and CRC cases, respectively, but accounted for 9.4% and 14.1% out of 575 GC and 205 CRC cases, respectively, excluding unequivocal microsatellite stable/MSI-low and MMR-proficient (pMMR) expression cases. pMMR expression was observed in most of the MSI-H GCs and CRCs consisting of only one unstable BAT-25 mononucleotide marker or solely of dinucleotide markers. ConclusionsConsidering the low incidence of MSI-H or dMMR expression, discordant or indeterminate IHC and/or MSI results were occasionally identified in GC and CRC cases, requiring complementary testing. These findings provide evidence for MSI testing and MMR IHC in routine clinical practice.

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