A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Systemic circulating microRNA landscape in Lynch syndrome (2023)


Sievänen, T., Korhonen, T., Jokela, T., Ahtiainen, M., Lahtinen, L., Kuopio, T., Lepistö, A., Sillanpää, E., Mecklin, J., Seppälä, T. T., & Laakkonen, E. K. (2023). Systemic circulating microRNA landscape in Lynch syndrome. International Journal of Cancer, 152(5), 932-944. https://doi.org/10.1002/ijc.34338


JYU-tekijät tai -toimittajat


Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajatSievänen, Tero; Korhonen, Tia‐Marje; Jokela, Tiina; Ahtiainen, Maarit; Lahtinen, Laura; Kuopio, Teijo; Lepistö, Anna; Sillanpää, Elina; Mecklin, Jukka‐Pekka; Seppälä, Toni T.; et al.

Lehti tai sarjaInternational Journal of Cancer

ISSN0020-7136

eISSN1097-0215

Julkaisuvuosi2023

Ilmestymispäivä25.10.2022

Volyymi152

Lehden numero5

Artikkelin sivunumerot932-944

KustantajaWiley

JulkaisumaaYhdysvallat (USA)

Julkaisun kielienglanti

DOIhttps://doi.org/10.1002/ijc.34338

Julkaisun avoin saatavuusAvoimesti saatavilla

Julkaisukanavan avoin saatavuusOsittain avoin julkaisukanava

Julkaisu on rinnakkaistallennettu (JYX)https://jyx.jyu.fi/handle/123456789/83820

LisätietojaCorrection: International Journal of Cancer 2024, 154(7), E6-E8, https://doi.org/10.1002/ijc.34828


Tiivistelmä

Circulating microRNAs (c-miRs) are small non-coding RNA molecules that migrate throughout the body and regulate gene expression. Global c-miR expression patterns (c-miRnomes) change with sporadic carcinogenesis and have predictive potential in early detection of cancers. However, there are no studies that have assessed whether c-miRnomes display similar potential in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), known as Lynch syndrome (LS), who are predisposed to highly increased cancer risk. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers, sporadic rectal cancer patients and non-LS controls. We showed for the first time that cancer-free path_MMR carriers have a systemic c-miRnome of 40 differentially expressed c-miRs that can distinguish them from non-LS controls. The systemic c-miRnome of cancer-free path_MMR carriers also resembles the systemic c-miRnomes of cancer patients with or without path_MMR. Our pathway analysis linked the found differentially expressed c-miRs to carcinogenesis. A total of 508 putative target genes were identified for 32 out of 40 differentially expressed c-miRs, and 238 of them were enriched in cancer-related pathways. The most enriched c-miR-target genes include well-known oncogenes and tumor suppressor genes such as BCL2, AKT3, PIK3CA, KRAS, NRAS, CDKN1A and PIK3R1. Taken together, our findings suggest that LS and sporadic carcinogenesis share common biological pathways and alterations in these pathways can produce a c-miR signature which can track potential oncogenic stress in cancer-free path_MMR carriers. Therefore, c-miRs hold potential in monitoring the LS risk stratification patterns during clinical surveillance or cancer management.


YSO-asiasanatbioinformatiikkaperinnölliset tauditsyöpätauditsuolistosyövätLynchin oireyhtymämikro-RNAsekvensointi

Vapaat asiasanathereditary cancer; next generation sequencing


Liittyvät organisaatiot


Hankkeet, joissa julkaisu on tehty


Liittyvät tutkimusaineistot


OKM-raportointiKyllä

VIRTA-lähetysvuosi2023

JUFO-taso2


Viimeisin päivitys 2024-12-10 klo 15:30