Impact of MiRSNPs on Survival and Progression in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Larrea, Carlos Fernández de; Navarro, Alfons; Tejero, Rut; Tovar, Natalia; Díaz, Tania; Cibeira, María Teresa; Rosiñol, Laura; Ferrer, Gerardo; Rovira, Montserrat; Rozman, Marı́a; Monzó, Mariano; Bladé, Joan

doi:10.1158/1078-0432.ccr-12-0191

Cited by 52 publications

(56 citation statements)

References 23 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…XPO5 inactivation resulted in reduced miRNA processing and decreased miRNA target inhibition, while the restored XPO5 reverses the impaired export of pre-miRNA (24). The miR-SNP of rs11077 of XPO5 has been identified for its association with the cancer risk of esophageal cancer as well as the outcome of myeloma (20,25). The mechanism of how this SNP affects SCLC survival remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Additionally, the RNA-induced silencing complex (RISC) including GEMIN3 and GEMIN4 selects a single strand as the mature miRNA and guides the mature miRNAs to their target mRNA sites (10,13-16). miRNA-related single nucleotide polymorphisms (miR-SNPs), defined as SNPs in miRNA genes, miRNA binding site and miRNA processing machinery, are able to modulate miRNA and target gene expressions in order to influence cancer risk, treatment efficacy and patient prognosis (9,(17)(18)(19)(20).A miR-SNP of rs11077 located in the 3'UTR of the miRNA processing gene XPO5 has shown its association with the chemotherapeutic response in metastatic colon cancer as well as recurrence in resected non-small cell lung cancer (NSCLC) (9,19). In the present study, we evaluated the predictive power of this SNP on the overall survival of SCLC patients.…”

mentioning

confidence: 99%

See 2 more Smart Citations

A microRNA-related single nucleotide polymorphism of the XPO5 gene is associated with survival of small cell lung cancer patients

Guo

Wang

et al. 2013

Biomedical Reports

View full text Add to dashboard Cite

Abstract. MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA processing machinery genes affect cancer risk, treatment efficacy and patient prognosis. A miR-SNP of rs11077 located in the 3'UTR of miRNA processing machinery gene XPO5 was examined in small cell lung cancer (SCLC) patients to evaluate its association with cancer survival. A total of 42 patients were enrolled in the present study and genotyped for rs11077 and survival was assessed using the Kaplan-Meier method, as well as univariate and multivariate analyses. The AA genotype of rs11077 was identified for its significant association with better survival time (P=0.023). In addition, rs11077 was found to associate independently with overall survival in SCLC patients by multivariate analysis (relative risk 2.469; 95% CI, 1.088-5.603; P=0.031). The findings of this study suggest that although miR-SNP studies for miRNA processing machinery genes are still at an early age, miR-SNPs have an impact on cancer survival. In conclusion, a miR-SNP in the 3'UTR region of the XPO5 gene was identified as an independent prognostic marker for survival of advanced SCLC patients. IntroductionSmall cell lung cancer (SCLC), commonly classified by the Veterans Administration Lung Cancer Study Group as Limited stage and Extensive stage groups, constitutes ~15% of all lung cancer cases and is strongly associated with cigarette smoking (1-3). The prognosis of SCLC, which has been associated with extent of disease and other factors, is poor, whereas the life expectancy of those with untreated SCLC is ~3.5 months for the limited stage group and 6 weeks for the extensive stage group (4-6). Although genetic factors have been identified as prognostic factors for SCLC, the underlying mechanism of this cancer remains unknown (7-9).MicroRNAs (miRNAs) are RNA molecules that are ~22 nucleotides long and are involved in various biological processes, such as embryonic development, cell differentiation, proliferation, apoptosis, cancer development and insulin secretion (10,11). More than 700 miRNAs have been identified in humans and these miRNAs are responsible for regulating at least 30% of protein-coding gene expressions (12). A growing body of evidence suggests that miRNAs play important roles in a broad range of biological processes, as previously mentioned (9-11). In the miRNA processing, long primary transcripts of miRNAs (pri-miRNAs) are processed in the nucleus by RNase III Drosha and transported to the cytoplasm by the nuclear transport factor exportin-5 (XPO5) and RAN. In the cytoplasm, RNase III Dicer and transactivation-responsive RNA-binding protein (TRBP) mediate the processing of pre-miRNAs in order to release a 21-bp dsRNA. Additionally, the RNA-induced silencing complex (RISC) including GEMIN3 and GEMIN4 selects a single strand as the mature miRNA and guides the mature miRNAs to their target mRNA sites (10,13-16). miRNA-related single nucleotide polymorphisms (miR-SNPs), defined as SNPs in miRNA genes, miRNA binding site and miRNA processing machi...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

A microRNA-related single nucleotide polymorphism of the XPO5 gene is associated with survival of small cell lung cancer patients

Guo

Wang

et al. 2013

Biomedical Reports

View full text Add to dashboard Cite

show abstract

“…Not examined in this study [24] rs6877842 G/C Multiple myeloma (137) AC and CC associated with longer PFS (p = 0.013) and OS (p = 0.012) after ASCT C allele decreased luciferase levels, CC genotype was associated with slightly reduced protein levels in healthy lymphocytes [30] rs7755135 C/T Childhood ALL (129) CT and TT associated with higher incidence of mucositis (2.68 (1.14-6.32), p = 0.0251) Not examined in this study; SNP in 3 UTR with potential effect on miRNA binding, T allele predicted to create binding site for miR-768-3p [24] rs34324334 C/T Childhood ALL (128) CT associated with higher incidence of hyperbilirubinemia (7.77 (2.35-25.7), p = 0.0011) Not examined in this study [24] ASCT, autologous stem cell transplantation; ALL, acute lymphoblastic leukemia; DFS, disease-free survival; HL, Hodgkin lymphoma; OR (95% CI), odds ratio (95% confidence interval); OS, overall survival; PFS, progression-free survival. Uncorrected p values for multiple testing are given.…”

Section: Snps In the Genes Of The Drosha Complexmentioning

confidence: 87%

MicroRNA polymorphisms as markers of risk, prognosis and treatment response in hematological malignancies

Dzikiewicz‐Krawczyk

2015

Critical Reviews in Oncology/Hematology

View full text Add to dashboard Cite

“…37 Polymorphisms related to miRNAs (miRSNPs) also have a prognostic impact in myeloma, and two miRSNPs-KRT81 and XPO5-are prognostic after melphalan-based autologous stem-cell transplantation. 51 The precise role of miRNAs in myeloma needs to be further elucidated, although they are predicted to be involved in PC growth, survival, growth factor response, homing, drug resistance and BM interaction.…”

mentioning

confidence: 99%

MicroRNA theragnostics for the clinical management of multiple myeloma

et al. 2013

View full text Add to dashboard Cite

Theragnostics represent cutting-edge, multi-disciplinary strategies that combine diagnostics with therapeutics in order to generate personalized therapies that improve patient outcome. In oncology, the approach is aimed at more accurate diagnosis of cancer, optimization of patient selection to identify those most likely to benefit from a specific therapy and to generate effective therapeutics that enhance patient survival. MicroRNAs (miRNAs) are master regulators of the human genome that orchestrate myriad cellular pathways to control growth during physiologic and pathologic conditions. Compelling evidence shows that miRNA deregulation promotes events linked to tumor initiation, metastasis and drug resistance as seen in multiple myeloma (MM), an invariably fatal hematologic malignancy. miRNAs are readily detected in body fluids, for example, serum, plasma, urine, as well as circulating tumor cells to demonstrate their potential as readily accessible, non-invasive diagnostic and prognostic biomarkers and potential therapeutics. Specific miRNAs are aberrantly expressed early in myelomagenesis and may more readily detect high-risk disease than current methods. Although only recently discovered miRNAs have rapidly advanced from preclinical studies to evaluation in human clinical trials. The development of miRNA theragnostics should provide widely applicable tools for the targeted delivery of personalized medicines to improve the outcome of patients with MM.

show abstract

Impact of MiRSNPs on Survival and Progression in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Cited by 52 publications

References 23 publications

A microRNA-related single nucleotide polymorphism of the XPO5 gene is associated with survival of small cell lung cancer patients

A microRNA-related single nucleotide polymorphism of the XPO5 gene is associated with survival of small cell lung cancer patients

MicroRNA polymorphisms as markers of risk, prognosis and treatment response in hematological malignancies

MicroRNA theragnostics for the clinical management of multiple myeloma

Contact Info

Product

Resources

About