Počet záznamů: 1
MiR-140 leads to MRE11 downregulation and ameliorates oxaliplatin treatment and therapy response in colorectal cancer patients
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SYSNO ASEP 0567833 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název MiR-140 leads to MRE11 downregulation and ameliorates oxaliplatin treatment and therapy response in colorectal cancer patients Tvůrce(i) Horák, Josef (UEM-P) ORCID
Dolníková, Alexandra (UEM-P)
Cumaogullari, O. (TR)
Čumová, Andrea (UEM-P)
Navvabi, Nazila (UEM-P)
Vodičková, Ludmila (UEM-P) RID
Levý, M. (CZ)
Schneiderová, M. (CZ)
Liška, V. (CZ)
Anděra, Ladislav (BTO-N)
Vodička, Pavel (UEM-P) RID
Opattová, Alena (UEM-P)Číslo článku 959407 Zdroj.dok. Frontiers in Oncology. - : Frontiers Research Foundation - ISSN 2234-943X
Roč. 12, oct (2022)Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova miR-140 ; colorecal cancer ; MRE11 ; oxaliplatin ; therapy response ; DNA damage ; DNA repair ; miRNA Obor OECD Oncology CEP GA20-03997S GA ČR - Grantová agentura ČR GA21-27902S GA ČR - Grantová agentura ČR GX21-04607X GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora UEM-P - RVO:68378041 ; BTO-N - RVO:86652036 UT WOS 000877974100001 EID SCOPUS 85140954325 DOI 10.3389/fonc.2022.959407 Anotace Cancer therapy failure is a fundamental challenge in cancer treatment. One of the most common reasons for therapy failure is the development of acquired resistance of cancer cells. DNA-damaging agents are frequently used in first-line chemotherapy regimens and DNA damage response, and DNA repair pathways are significantly involved in the mechanisms of chemoresistance. MRE11, a part of the MRN complex involved in double-strand break (DSB) repair, is connected to colorectal cancer (CRC) patients' prognosis. Our previous results showed that single-nucleotide polymorphisms (SNPs) in the 3 ' untranslated region (3 ' UTR) microRNA (miRNA) binding sites of MRE11 gene are associated with decreased cancer risk but with shorter survival of CRC patients, which implies the role of miRNA regulation in CRC. The therapy of colorectal cancer utilizes oxaliplatin (oxalato(trans-l-1,2-diaminocyclohexane)platinum), which is often compromised by chemoresistance development. There is, therefore, a crucial clinical need to understand the cellular processes associated with drug resistance and improve treatment responses by applying efficient combination therapies. The main aim of this study was to investigate the effect of miRNAs on the oxaliplatin therapy response of CRC patients. By the in silico analysis, miR-140 was predicted to target MRE11 and modulate CRC prognosis. The lower expression of miR-140 was associated with the metastatic phenotype (p < 0.05) and poor progression-free survival (odds ratio (OR) = 0.4, p < 0.05). In the in vitro analysis, we used miRNA mimics to increase the level of miR-140 in the CRC cell line. This resulted in decreased proliferation of CRC cells (p < 0.05). Increased levels of miR-140 also led to increased sensitivity of cancer cells to oxaliplatin (p < 0.05) and to the accumulation of DNA damage. Our results, both in vitro and in vivo, suggest that miR-140 may act as a tumor suppressor and plays an important role in DSB DNA repair and, consequently, CRC therapy response. Pracoviště Ústav experimentální medicíny Kontakt Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Rok sběru 2023 Elektronická adresa https://www.frontiersin.org/articles/10.3389/fonc.2022.959407/full
Počet záznamů: 1