Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells

Song, Bo; Wang, Yuan; Xi, Yaguang; Kudo, Kenji; Bruheim, Skjalg; Botchkina, Galina I.; Gavin, Elaine; Wan, Yu; Formentini, A.; Kornmann, Marko; Fodstad, Øystein; Ju, Jingfang

doi:10.1038/onc.2009.274

Cited by 372 publications

(302 citation statements)

References 38 publications

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“…In two studies by Song et al (34,35), miR-140 and -215 were found to be overexpressed in drug-resistant colorectal cancer cell lines. On the basis of their findings, these miRNAs correlated with resistance to the anticancer drugs methotrexate, 5-fluorouacil, and tomudex.…”

Section: Micrornas As Biomarkers For Chemoresistancementioning

confidence: 99%

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Resistance May Not Be Futile: microRNA Biomarkers for Chemoresistance and Potential Therapeutics

Allen

Weiss

2010

Molecular Cancer Therapeutics

140

111

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Chemoresistance to many commercially available cancer therapeutic drugs is a common occurrence and contributes to cancer mortality as it often leads to disease progression. There have been a number of studies evaluating the mechanisms of resistance and the biological factors involved. microRNAs have recently been identified as playing a role in the regulation of key genes implicated as cancer therapeutic targets or in mechanisms of chemoresistance including EGFR, MDR1, PTEN, Bak1, and PDCD4 among others. This article briefly reviews chemoresistance mechanisms, discusses how microRNAs can play a role in those mechanisms, and summarizes current research involving microRNAs as both regulators of key target genes for chemoresistance and biomarkers for treatment response. It is clear from the accumulating literature that microRNAs can play an important role in chemoresistance and hold much promise for the development of targeted therapies and personalized medicine. This review brings together much of this new research as a starting point for identifying key areas of interest and potentials for future study.

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Section: Micrornas As Biomarkers For Chemoresistancementioning

confidence: 99%

“…On the basis of their findings, these miRNAs correlated with resistance to the anticancer drugs methotrexate, 5-fluorouacil, and tomudex. In addition, an analysis of possible protein targets for these miRNAs pointed to HDAC4 and DHFR, respectively (34,35).…”

Section: Micrornas As Biomarkers For Chemoresistancementioning

confidence: 99%

Resistance May Not Be Futile: microRNA Biomarkers for Chemoresistance and Potential Therapeutics

Allen

Weiss

2010

Molecular Cancer Therapeutics

140

111

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“…A number of miRNAs, including miR-140 and miR-215, have been shown to regulate osteosarcoma chemoresistance. 45,46 Ectopic miR-215 protected osteosarcoma and colon cancer cell lines from methotrexate (MTX) and Tomudex, whereas miR-140 overexpression desensitized osteosarcoma cells to MTX and 5-fluorouracil. More recently, miRNA expression analysis of chemoresistant patient samples and cell lines revealed a miRNA signature consisting of miR-92a, -99b, -132, -193a-5p and -422a that was capable of predicting response to ifosfamide, whereas miR-33a reduced cisplatin-induced apoptosis.…”

Section: Mirna Expression Influences Growth and Progression Of Osteosmentioning

confidence: 99%

MicroRNAs as regulators of bone homeostasis and bone metastasis

Ell

Kang

2014

Bonekey Reports

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MicroRNAs (miRNAs) are short, endogenous RNAs that have essential roles in regulating gene expression through the disruption of target genes. The miRNA-induced suppression can occur through Argonaute-mediated cleavage of target mRNAs or by translational inhibition. System-wide studies have underscored the integral role that miRNAs play in regulating the expression of essential genes within bone marrow stromal cells. The miRNA expression has been shown to enhance or inhibit cell differentiation and activity, and elucidating miRNA targets within bone marrow cells has revealed novel regulations during normal bone development. Importantly, multiple studies have shown that miRNA misexpression mediates the progression of bone-related pathologies, including osteopetrosis and osteoporosis, as well as the development and progression of osteosarcoma. Furthermore, recent studies have detailed the capacity for miRNAs to influence bone metastasis from a number of primary carcinomas. Taken together, these findings reveal the significant clinical potential for miRNAs to regulate bone homeostasis, as well as to mediate bone-related pathologies.BoneKEy Reports 3, Article number: 549 (2014) | doi:10.1038/bonekey.2014.44 MiRNA Biogenesis and FunctionThe past decade has seen a torrent of novel research into the post-translational regulation of genes via microRNA-mediated suppression. The microRNAs (miRNAs) are a class of B22-nucleotide-long RNAs that repress gene expression through complementary binding to sites in the 3 0 -untranslated region (UTR) of target mRNAs. 1 Mature miRNAs are generated by the sequential cleavage of longer precursor transcripts, or pri-miRNAs, that are typically transcribed from intragenic or intergenic regions by RNA polymerase II. 2 The initial cleavage step, mediated by Drosha and the DGCR8 complex, occurs in the nucleus and produces a shortened (70-100 nucleotides) pre-miRNA hairpin. Pre-miRNAs are exported from the nucleus by Exportin 5, followed by a second cleavage by the ribonuclease Dicer that produces a double-stranded, B18-25-nucleotide-long mature miRNA. One miRNA strand will then combine with Argonaute (AGO2) proteins to produce an RNAinduced silencing complex, allowing for directed pairing with target mRNAs. 1

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“…It has been reported that several miRNAs were misregulated in osteosarcoma tissues or cells, such as miR-34, miR-21, miR-140, miR-223 and miR-195 (He et al, 2009;Song et al, 2009;Wu et al, 2011;Mao et al, 2012;Li et al, 2012;Zhao et al, 2013). For instance, expression of miR-34s was decreased in tumor samples, and MiR-34 genes underwent minimal deletions and epigenetic inactivation in osteosarcomas ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-802 Promotes Osteosarcoma Cell Proliferation by Targeting p27

Cao¹,

Shen²,

Huang³

2013

Asian Pacific Journal of Cancer Prevention

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MicroRNAs have been demonstrated to regulate proliferation and apoptosis in many types of cancers, but biological functions in osteosarcomas remain relatively unknown. Here, we found expression of miR-802 to be up-regulated in osteosarcoma tissues in comparison with adjacent normal tissues. Enforced expression of miR-802 was able to promote cell proliferation in U2OS and MG63 cells, while miR-802 antisense oligonucleotides (antisense miR-802) inhibited cell proliferation. At the molecular level, our results further revealed that expression of p27, a negative cell-cycle regulator, was negatively regulated by miR-802. Therefore, the data reported here indicate that miR-802 is an important regulator in osteosarcoma, our findings contributing to a better understanding of important mis-regulated miRNAs in this tumour type.

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Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells

Cited by 372 publications

References 38 publications

Resistance May Not Be Futile: microRNA Biomarkers for Chemoresistance and Potential Therapeutics

Resistance May Not Be Futile: microRNA Biomarkers for Chemoresistance and Potential Therapeutics

MicroRNAs as regulators of bone homeostasis and bone metastasis

MicroRNA-802 Promotes Osteosarcoma Cell Proliferation by Targeting p27

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