Ugotavljanje vloge dolgih nekodirajočih RNA pri nastanku, diagnosticiranju in zdravljenju trojno negativnega raka dojk

Košir, Tamara (author), Pajič, Tadej (mentor), Kunej, Tanja (comentor)

Trojno negativni rak dojk (TNBC) je najbolj agresivni molekularni podtip raka dojk (BC), ki se od drugih razlikuje po negativnem stanju tumorskih celic za estrogenski (ER) in progesteronski (PR) receptor ter receptor 2 za humani epidermalni rastni faktor (HER2). Bolezen pogosto odkrijemo v poznem kliničnem stadiju. Zaradi odsotnosti receptorjev in tako molekularnih tarč za ciljano zdravljenje, je zdravljenje omejeno na sistemsko kemoterapijo, na katero lahko tumorji razvijejo odpornost. Posledično se več raziskav usmerja v iskanje novih tarč za diagnosticiranje in zdravljenje TNBC. Med njimi se preiskuje tudi dolge nekodirajoče RNA (lncRNA) z diferencialnim izražanjem. Pomemben del tovrstnega raziskovanja je sistematično zbiranje in urejanje informacij o izražanju lncRNA v tkivih, njihovem mehanizmu delovanja ter tarčah. Pri tem so ključne različne podatkovne zbirke, ki so nepopolne in redko posodobljene, med podatki pa so prisotne neskladnosti, kar zmanjša njihovo uporabno vrednost. Namen raziskave je tako bil ustvariti zbirko lncRNA z diferencialnim izražanjem specifično pri TNBC (TNBClncRNAdb). Zbirko TNBClncRNAdb, ki obsega 241 vnosov, vezanih na 187 lncRNA, smo osnovali na podatkih iz petih predhodno obstoječih zbirk ter jo nadgradili z najnovejšo znanstveno literaturo. Dopolnili smo jo s podatki, kot so simboli in sinonimi lncRNA, njihovo diferencialno izražanje v preučevanih tkivih in mehanizem delovanja ter njihove direktne in indirektne tarče. Kot razširitev TNBClncRNAdb smo oblikovali zbirko OnCoLocDB, ki vključuje 437 vnosov, vezanih na 438 genov, s katerimi si lncRNA geni delijo genomsko lokacijo (co-loc geni), ter informacije o njihovem biotipu, genomski lokaciji ter potencialni vlogi pri nastanku raka. Zaključili smo, da imajo lncRNA potencial kot biooznačevalci pri diagnosticiranju TNBC ter kot tarče pri njegovem zdravljenju. Hkrati smo ugotovili, da se lncRNA geni prekrivajo s co-loc geni z vlogo pri nastanku raka ter da hkrati uravnavajo njihovo izražanje. Oblikovani zbirki sta informativni ter lahko kot prvi zbirki, specifični za TNBC, služita kot temelj za razvoj naprednih postopkov njegovega diagnosticiranja in zdravljenja.

• Language: Slovenian
• Keywords: dolge nekodirajoče RNA, lncRNA, trojno negativni rak dojk, rak dojk, podatkovna zbirka, sistematična analiza podatkov, podatkovno rudarjenje
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: BF - Biotechnical Faculty
• Year: 2024
• PID: 20.500.12556/RUL-164525
• COBISS.SI-ID: 213466627
• Publication date in RUL: 30.10.2024

Secondary language

• Language: English
• Title: Establishing roles of long-noncoding RNAs (lncRNAs) in development, diagnosis, and treatment of triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is considered the most aggressive molecular subtype of breast cancer (BC), characterized by the tumours' negative status for estrogen (ER) and progesterone (PR) receptors and human epidermal growth factor receptor 2 (HER2). The issue of this disease is two-fold; it is often diagnosed in its later stages, while, due to the absence of receptors, its treatment is limited to systemic chemotherapy, which has a high chance of inducing resistance in tumours. This further highlights the need for determination of novel targets for diagnosis and treatment of TNBC, with differentially expressed long non-coding RNAs (lncRNAs) showing high potential. To develop these novel approaches to treatment, systematic gathering and analysis of disease-specific data on lncRNAs is required. However, currently available databases are inconsistent, rarely updated with novel data, and have other limitations such as not being standardized. Therefore, the objective of this study was to design the first TNBC-specific database of differentially expressed lncRNAs (TNBClncRNAdb). The database TNBClncRNAdb includes 241 entries corresponding to 187 different lncRNAs. It was based on data collected from five existing databases, and updated with novel scientific literature. It includes information on lncRNAs, such as their approved symbols and aliases, their differential expression and molecular mechanism of regulation, and their direct and indirect downstream targets. The database OnCoLocDB was also designed, which serves as an expansion of TNBClncRNAdb and includes a list of genes, co-located with lncRNA genes (co-loc genes), their biotype, genome location, and possible role in cancer development. We concluded that lncRNAs show a high potential as biomarkers in diagnosis of TNBC, and as targets in its treatment. We also concluded that lncRNA genes overlap with co-loc genes with a role in cancer development, and regulate their expression. So-designed databases are informative and TNBC-specific and can, therefore, serve as a foundation for development of novel diagnostic and treatment procedures, targeting differentially expressed lncRNAs.

• Keywords: long non-coding RNA, lncRNA, triple-negative breast cancer, breast cancer, database, systematic data analysis, data mining