Characterizing the Protein Coding RNAs (mRNA) and Long Non-Coding RNAs (LncRNAs) in Chemo Resistant Triple Negative Breast Cancer

Breast Cancer (BC) is the most diagnosed cancer type in both genders according to the world health organization. While the five-year survival rate of cases diagnosed with early-stage localized BC is about 99%, this number drastically drop for advanced and metastatic cases. Treatment of BC is dependent on its molecular subtype. Majority of BC overexpress estrogen and progesterone receptors or epidermal growth factor receptors and are referred to as HR+ or HER2+, respectively. Triple negative Breast cancer (TNBC) is another type of BC characterized by the lack of HR and HER2 overexpression. Although, death rates due to BC have consistently decreased over time, TNBC still poses a challenge due to its poor prognosis, high rates of relapse and resistance to chemotherapy. In current study, we investigated the expression of protein coding messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in doxorubicin-resistant MDA-MB-231 cell model. Expression data were subjected to differential, principal component, and hierarchical clustering analyses. Findings from our in vitro model were then validated using RNA-Seq data from the PRJNA607780 xenograft dataset. Using comparative and bioinformatics analyses, we identified the transcriptional landscape associated with doxorubicin resistance in TNBC. Our data highlighted cytokines and inflammatory response as the hallmark of doxorubicin resistance. Nonetheless, NEAT1 and MALAT1 lncRNAs were among the identified upregulated lncRNAs in response to doxorubicin treatment. Understanding the mechanism by which these transcriptomic alterations contribute to chemotherapy resistance and their prognostic and therapeutic potential in TNBC remains to be investigated.