Identification of miRSNPs associated with the risk of multiple myeloma

Macauda, Angelica; Calvetti, Diego; Maccari, Giuseppe; Hemminki, Kari; Försti, Asta; Goldschmidt, Hartmut; Weinhold, Niels; Houlston, Richard S.; Andersen, Vibeke; Vogel, Ulla; Buda, Gabriele; Várkonyi, Judit; Sureda, Anna; Martínez‐López, Joaquín; Wątek, Marzena; Butrym, Aleksandra; Sarasquete, María Eugenia; Dudziński, Marek; Jurczyszyn, Artur; Druzd‐Sitek, Agnieszka; Kruszewski, Marcin; Subocz, Edyta; Petrini, Mario; Iskierka‐Jażdżewska, Elżbieta; Raźny, Małgorzata; Szombath, Gergely; Marques, Herlander; Zawirska, Daria; Chraniuk, Dominik; Hałka, Janusz; Jacobsen, Svend Erik Hove; Mazur, Grzegorz; Sanz, Ramón Garcí­a; Dumontet, Charles; Stępień, Anna; Beider, Katia; Pelosini, Matteo; Reis, Rui Manuel; Krawczyk-Kuliś, Małgorzata; Rymko, Marcin; Avet-Loiseau, Hervé; Lesueur, Fabienne; Grząśko, Norbert; Ostrovsky, Olga; Jamroziak, Krzysztof; Vangsted, Annette Juul; Jerez, Andrés; Tomczak, Waldemar; Zaucha, Jan Maciej; Kádár, Katalin; Sainz, Juan; Nagler, Arnon; Landi, Stefano; Gemignani, Federica; Canzian, Federico

doi:10.1002/ijc.30465

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…Our previous data reported significant associations between p3UTRs within DDR1 , TCF19 and POU5F1 genes, and increased risk of developing MM, 18 highlighting the importance of association studies in discovering novel variants associated with MM pathogenesis. Herein, we expanded the investigation by evaluating the association between p3UTRs of candidate genes, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496) with MM risk and prognosis.…”

Section: Discussionmentioning

confidence: 91%

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Common gene variants within 3′‐untranslated regions as modulators of multiple myeloma risk and survival

Macauda

Sáinz

Calvetti

et al. 2020

Intl Journal of Cancer

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We evaluated the association between germline genetic variants located within the 3′‐untranlsated region (polymorphic 3′UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case‐control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10‐rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3′‐UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A‐allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10‐rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis.

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Section: Discussionmentioning

confidence: 91%

“…within DDR1, TCF19 and POU5F1 genes, and increased risk of developing MM, 18 IL-10 has been identified as an anti-inflammatory cytokine. In macrophages, it inhibits the expression of inflammatory cytokines (such as INF-γ, IL-2, IL-3 and TNF-α) and deactivates their functions.…”

Section: Discussionmentioning

confidence: 99%

Common gene variants within 3′‐untranslated regions as modulators of multiple myeloma risk and survival

Macauda

Sáinz

Calvetti

et al. 2020

Intl Journal of Cancer

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“…Multiple transcriptome modifiers play a critical role in determining growth and survival of cancer cells, including MM cells [5, 6]. These modifiers include small non-coding RNAs such as miRs, and a large repertoire of molecules involved in pre-mRNA/mRNA processing [9, 11, 43, 44]. In this study, we delineate the interplay between these two processes in MM cells.…”

Section: Discussionmentioning

confidence: 99%

The effects of MicroRNA deregulation on pre-RNA processing network in multiple myeloma

et al. 2019

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Over the last few years, a detailed map of genetic and epigenetic lesions that underlie multiple myeloma (MM) has been created. Regulation of microRNA (miR)-dependent gene expression and mRNA splicing play significant roles in MM pathogenesis; however, to date an interplay between these processes is not yet delineated. Here we investigated miR-mediated regulation of splicing networks at the transcriptome level. Our studies show that a significant number (78%) of miRs which are either up- or down-regulated in patient CD138+ MM cells, but not in healthy donors (HD) CD138+ plasma cells (PC), target genes involved in early stages of pre-mRNA splicing. We also identified deregulated miRs that target core splicing factors (SF) and modifiers (SM, enhancers/silencers) which cause altered splicing in MM. Our studies suggest that Let-7f, in combination other miRs which are frequently and significantly deregulated in patients with overt MM, targets genes that regulate intron excision. Importantly, deregulated expression of certain miRs in MM promote increased intron retention, a novel characteristic of the MM genome, by inducing deregulated expression of the genes that regulate the splicing network. Our studies, therefore, provide the rationale for therapeutically targeting deregulated miRs to reverse aberrant splicing and improve patient outcome in MM.

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“…The OCT4 rs13409CC and OCT4 rs3130932GG genotypes were also found to be risk factors for lung cancer. OCT4 rs13409 showed [34] a significant association with multiple myeloma risk in 1,832 controls and 2,894 MM from seven European countries and Israel. In northern Iran [35], the OCT4 rs3130932G allele was associated with the incidence of gastric cancer; genotypes AC [P = 0 031, OR = 0 63 (0.44-0.91)] and AC+CC [P = 0 031, OR = 0 68 (0.48-0.95)] had protective effects on patients in north India [36].…”

Section: Disease Markersmentioning

confidence: 95%

Association of Single-Nucleotide Polymorphism REX1 rs6815391, OCT4 rs13409 or rs3130932, and CTBP2 rs3740535 with Primary Lung Cancer Susceptibility: A Case-Control Study in a Chinese Population

Shen

Wang

et al. 2019

Disease Markers

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The purpose of the current study is to explore the contribution of single-nucleotide polymorphisms (SNPs) of REX1 rs6815391, OCT4 rs13409 or rs3130932, and CTBP2 rs3740535 to the risk of lung cancer. A questionnaire survey was used to obtain basic information of the included subjects. A case control study was performed in 1121 patients and 1121 controls. All subjects were subjected to blood sampling for genomic DNA extraction and genotyping of the cancer stem cell-associated gene SNPs, including REX1 rs6815391, OCT4 rs13409 or rs3130932, and CTBP2 rs3740535 by real-time PCR. The association with the risk of primary lung cancer and interaction with environmental factors were assessed using unconditional logistic regression for the odds ratios and corresponding 95% confidence intervals. The genotype frequency distribution of OCT4 rs13409 loci was statistically significant, but there was no significant difference in the rest of the loci between lung cancer patients and healthy controls. The OCT4 gene was also related with lung cancer susceptibility in the genetic model after adjusting for lung cancer-related factors. Despite the presence of the dominant or recessive model, the four loci polymorphisms were associated with pollution near the place of residence, house type, worse ventilation situation, smoking, passive smoking, cooking oil fumes (COF), and family history of cancer, which increased the risk of lung cancer. Nonmarried status, 18.5≤BMI, COF, smoking, passive smoking, family history of cancer, and history of lung disease were independent risk factors of lung cancer susceptibility. Additionally, college degree or above, no pollution near the place of residence, protective genotype 1 or 2, and well ventilation can reduce the occurrence of lung cancer. There is an interaction between the four loci and environmental factors, and OCT4 rs13409 is a risk factor of primary lung cancer.

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Identification of miRSNPs associated with the risk of multiple myeloma

Cited by 8 publications

References 35 publications

Common gene variants within 3′‐untranslated regions as modulators of multiple myeloma risk and survival

Common gene variants within 3′‐untranslated regions as modulators of multiple myeloma risk and survival

The effects of MicroRNA deregulation on pre-RNA processing network in multiple myeloma

Association of Single-Nucleotide Polymorphism REX1 rs6815391, OCT4 rs13409 or rs3130932, and CTBP2 rs3740535 with Primary Lung Cancer Susceptibility: A Case-Control Study in a Chinese Population

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