Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells
Bo Song,Yuan Wang,Yuan Wang,Yaguang Xi,Kenji Kudo,Skjalg Bruheim,Galina I. Botchkina,Elaine Gavin,Yu Wan,Andrea Formentini,Marko Kornmann,Øystein Fodstad,Jingfang Ju +12 more
TLDR
Findings indicate that miR-140 is involved in the chemoresistance by reduced cell proliferation through G1 and G2 phase arrest mediated in part through the suppression of HDAC4.Abstract:
In this study, high-throughput microRNA (miRNA) expression analysis revealed that the expression of miR-140 was associated with chemosensitivity in osteosarcoma tumor xenografts. Tumor cells ectopically transfected with miR-140 were more resistant to methotrexate and 5-fluorouracil (5-FU). Overexpression of miR-140 inhibited cell proliferation in both osteosarcoma U-2 OS (wt-p53) and colon cancer HCT 116 (wt-p53) cell lines, but less so in osteosarcoma MG63 (mut-p53) and colon cancer HCT 116 (null-p53) cell lines. miR-140 induced p53 and p21 expression accompanied with G(1) and G(2) phase arrest only in cell lines containing wild type of p53. Histone deacetylase 4 (HDAC4) was confirmed to be one of the important targets of miR-140. The expression of endogenous miR-140 was significantly elevated in CD133(+hi)CD44(+hi) colon cancer stem-like cells that exhibit slow proliferating rate and chemoresistance. Blocking endogenous miR-140 by locked nucleic acid-modified anti-miR partially sensitized resistant colon cancer stem-like cells to 5-FU treatment. Taken together, our findings indicate that miR-140 is involved in the chemoresistance by reduced cell proliferation through G(1) and G(2) phase arrest mediated in part through the suppression of HDAC4. miR-140 may be a candidate target to develop novel therapeutic strategy to overcome drug resistance.read more
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Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers
TL;DR: Assessment of the colon cancer "epigenome" has revealed that virtually all CRCs have aberrantly methylated genes and altered miRNA expression, and progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC.
Journal ArticleDOI
Histone deacetylases and cancer.
TL;DR: The aim of this review is to summarize the current knowledge concerning the role of HDACs in cancer with special emphasis on what the authors have learned from the analysis of patient samples.
Journal ArticleDOI
miRNA Signatures Associate with Pathogenesis and Progression of Osteosarcoma
Kevin B. Jones,Zaidoun Salah,Sara Del Mare,Marco Galasso,Eugenio Gaudio,Gerard J. Nuovo,Francesca Lovat,Kimberly T. LeBlanc,Jeff Palatini,R. Lor Randall,Stefano Volinia,Gary S. Stein,Carlo M. Croce,Jane B. Lian,Rami I. Aqeilan +14 more
TL;DR: A miRNA signature associated with pathogenesis of osteosarcoma as well as critical pre-treatment biomarkers of metastasis and responsiveness to therapy is established.
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Targeting miRNAs involved in cancer stem cell and EMT regulation: An emerging concept in overcoming drug resistance
Zhiwei Wang,Yiwei Li,Aamir Ahmad,Asfar S. Azmi,Dejuan Kong,Sanjeev Banerjee,Fazlul H. Sarkar +6 more
TL;DR: A better understanding of the molecular intricacies of drug-resistant cells will help to design novel therapeutic strategies by selective targeting of CSCs and EMT-phenotypic cells through alterations in the expression of specific miRNAs towards eradicating tumor recurrence and metastasis.
Journal ArticleDOI
Interplay between microRNAs and the epigenetic machinery: an intricate network
TL;DR: This review will analyze and describe the regulatory loop interconnecting microRNAs and epigenetics, describing either how epigenetics can affect the miRNome, as well as how epi-miRNAs can control the epigenome, particularly focusing on the alterations observed in human cancer.
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