miR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis

Valencia, Karmele; Martín-Fernández, Marta; Zandueta, Carolina; Ormazábal, C.; Martínez-Canarias, Susana; Bandrés, Eva; Piedra, Concepción de la; Lecanda, Fernando

doi:10.1016/j.bone.2012.10.033

Cited by 44 publications

(39 citation statements)

References 34 publications

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“…In addition, miR-326 expression was shown to be downregulated in metastatic compared with non-metastatic primary loci in nude mouse NSCLC cells (66). Therefore, it may be possible to use miR-326 expression levels to monitor bone metastasis in patients with LAC (67). The results of the present study are consistent with a previous study, which demonstrated that high plasma expression of miR-27b, miR-148a and miR-326 prior to treatment with 5-fluorouracil and oxaliplatin was correlated with decreased PFS in patients with metastatic colorectal cancer (68).…”

Section: A B C Dsupporting

confidence: 91%

Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum

Zhu

et al. 2016

Oncology Letters

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Abstract. Pemetrexed combined with platinum is a first-line therapy used to treat patients with advanced non-small cell lung cancer (NSCLC) that exhibit negative or unknown epidermal growth factor receptor (EGFR) mutational status or anaplastic lymphoma kinase (ALK) rearrangements. Lung adenocarcinoma (LAC) is the primary type of NSCLC. In order to prevent overtreatment, it is necessary to identify patients with LAC who may not benefit from certain chemotherapies. Patients recruited in the present study (n=129) were diagnosed with advanced LAC and received first-line pemetrexed and platinum-based chemotherapy. A microRNA (miR) microarray was used to screen the plasma miR expression profiles in a screening set of eight patients prior to and following treatment. Specifically, plasma miR-25, miR-21, miR-27b, miR-326, miR-483-5p and miR-920 were selected for reverse transcription-quantitative polymerase chain reaction analysis in a training set (n=44) prior to treatment. The screening and training set patients were all non-smokers with no prior history of serious or chronic disease. The ∆∆Cq values of these miRs were compared between the group that showed benefit from pemetrexed and platinum treatment and the group that did not. Consequently, the ∆∆Cq values of miR-25, miR-21, miR-27b and miR-326 were further determined in a validation set (n=77). The results of the present study demonstrate that plasma expression levels of miR-25, miR-21, miR-27b and miR-326, in the training and validation sets prior to treatment, were significantly different between the benefit and non-benefit groups (P≤0.001). The expression of miR-25, miR-21, miR-27b and miR-326 was upregulated in the non-benefit group and this elevation was positively correlated with decreased progression-free survival (PFS; P≤0.001). In addition, the predictive power of each miR was evaluated through receiver operating characteristic curves, in which miR-25 exhibited the highest degree of accuracy (area under the curve, 0.926; 95% confidence interval, 0.881-0.971). These results indicate that overexpression of plasma miR-25, miR-21, miR-27b and miR-326, prior to treatment, in patients with advanced LAC is predictive of non-benefit from first-line pemetrexed and platinum-based chemotherapy, and is associated with decreased PFS. Among these four miRs, miR-25 exhibited the highest degree of accuracy in predicting insensitivity, suggesting it is the most promising biomarker.

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Section: A B C Dsupporting

confidence: 91%

Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum

Zhu

et al. 2016

Oncology Letters

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“…Of these 38 candidate miRNAs 25 have known human homologs, of which 11 have previously been identified to directly act in the metastatic cascade in various tumor types (let-7f, miR-30c, miR-31, miR-127, miR-134, miR-140, miR-148a, miR-196b, miR-210, miR-503, miR-582) (Valastyan et al 2009;Li et al 2010;Liang et al 2011;Ying et al 2011;Zhou and Wang 2011;Bockhorn et al 2013;Li et al 2013c;Liu et al 2013;Uchino et al 2013;Yang et al 2013a,b) while several other miRNAs have been associated with distant metastatic disease (miR-152, miR-298, miR-326, miR-423) (Farazi et al 2011;Bao et al 2012;Hui et al 2013;Valencia et al 2013). Moreover, as shown above, miR-140 and miR-582 were also found to contain a trans-eQTL (Table 2) implicating them as candidate heritable metastasis susceptibility miRNAs, which is consistent with the notion that these miRNAs target heritable metastasis susceptibility transcriptional networks.…”

Section: Integrated Analysis Of Gene Expression Profiling and Mirna Ementioning

confidence: 99%

An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease

Faraji

et al. 2013

Genome Res.

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Metastasis is the result of stochastic genomic and epigenetic events leading to gene expression profiles that drive tumor dissemination. Here we exploit the principle that metastatic propensity is modified by the genetic background to generate prognostic gene expression signatures that illuminate regulators of metastasis. We also identify multiple microRNAs whose germline variation is causally linked to tumor progression and metastasis. We employ network analysis of global gene expression profiles in tumors derived from a panel of recombinant inbred mice to identify a network of co-expressed genes centered on Cnot2 that predicts metastasis-free survival. Modulating Cnot2 expression changes tumor cell metastatic potential in vivo, supporting a functional role for Cnot2 in metastasis. Small RNA sequencing of the same tumor set revealed a negative correlation between expression of the Mir216/217 cluster and tumor progression. Expression quantitative trait locus analysis (eQTL) identified cis-eQTLs at the Mir216/217 locus, indicating that differences in expression may be inherited. Ectopic expression of Mir216/217 in tumor cells suppressed metastasis in vivo. Finally, small RNA sequencing and mRNA expression profiling data were integrated to reveal that miR-3470a/b target a high proportion of network transcripts. In vivo analysis of Mir3470a/b demonstrated that both promote metastasis. Moreover, Mir3470b is a likely regulator of the Cnot2 network as its overexpression down-regulated expression of network hub genes and enhanced metastasis in vivo, phenocopying Cnot2 knockdown. The resulting data from this strategy identify Cnot2 as a novel regulator of metastasis and demonstrate the power of our systems-level approach in identifying modifiers of metastasis.[Supplemental material is available for this article.]Metastasis is a systemic disease responsible for the majority of cancer-related mortality and is influenced by both tumor cell-autonomous and host-derived factors. Its complexity is deepened by involvement of not only stochastic genomic and epigenetic events but also by inherited predisposition (Lifsted et al. 1998;Crawford et al. 2006). As a result, despite identification and characterization of individual genes, cellular and developmental processes associated with metastasis, understanding of the metastatic cascade and the interconnectivity of individual factors remains limited. The elucidation of higher-order networks underlying metastasis will therefore likely improve prognostication and intervention strategies by identifying molecular nodes central to tumor cell dissemination and colonization.Recent advances in global gene expression profiling and computational science have provided the basis for understanding cancer biology at a systems level (Quigley et al. 2009). Knowledge of both tumor subtypes (Perou et al. 2000) and patient prognosis has been enhanced by systems-based approaches. This knowledge may significantly change clinical practice by enabling the development of precision treatments based on mol...

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“…56 The validity of measuring serum miRNAs in a murine model of human lung cancer bone metastasis has been assessed by comparing miRNA serum levels with those of standard biochemical markers of bone turnover such as PINP, BGP (osteocalcin) and CTX. 57 In this model of lung cancer, PINP exhibited a strong correlation with osteolytic lesions and tumour burden at early and late stages of bone colonisation. In contrast, BGP and CTX demonstrated a strong correlation only at late stages.…”

Section: Mirnas Regulate Bone Marrow Invasion and Colonisation By Canmentioning

confidence: 76%

“…These results suggest that miR-326 could serve as a biochemical marker for monitoring bone metastatic progression in advanced lung cancer. 57 MicroRNAs and bone metastasis M Croset et al…”

Section: Mirnas Regulate Bone Marrow Invasion and Colonisation By Canmentioning

confidence: 99%

Tumour-derived miRNAs and bone metastasis

Croset

Kan

Clézardin³

2015

BoneKEy Reports

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Skeletal metastases are complications of epithelial cancers, among which breast, prostate and lung carcinomas are the most osteotropic. In primary tumours, a subset of cancer cells undergoes epithelial-mesenchymal transition, acquires mobility to migrate into the surrounding stroma and seeds at distant sites to grow. The specific development of bone metastasis requires the recruitment of circulating tumour cells in the bone marrow, their adaptation to survive in the surrounding microenvironment where they alter the functions of osteoclasts and osteoblasts, and hijack signals coming from the bone matrix. Each of the molecular pathways underlining these steps is regulated by multiple factors, through the tight control of genes expressed by cancer cells interacting with cells from the bone microenvironment. In this context, miRNAs can act as master regulators of gene expression to control multiple aspects of bone metastasis formation, including cancer cell escape from the primary tumour site, cancer cell dissemination to bone and invasion of the bone marrow, as well as secondary outgrowth and tumour-stroma cell interactions. In the clinic, specific miRNA signatures have been identified in osteotropic cancer cells, raising the possibility that miRNAs could be used as biomarkers of bone metastasis. The regulatory activity of miRNAs in the bone microenvironment also suggests that miRNAs could be promising therapeutic targets.

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miR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis

Cited by 44 publications

References 34 publications

Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum

Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum

An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease

Tumour-derived miRNAs and bone metastasis

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