Long noncoding RNA TP۵۳TG۱ alteration impact on breast cancer progression

Backgrounds: Breast cancer is still one of leading causes of death in women worldwide. Themolecular mechanisms underlying the disease have been extensively studied focusing on proteincodinggenes. However, recent studies demonstrate that the majority of the genome is transcribedto non-coding RNAs (ncRNAs) which do not encode any protein.Materials and Methods: In this study, we examined ncRNAs in breast cancer patients and celllines using bioinformatics analysis and in vitro experiments. We focused on investigating theeffect of long non-coding RNAs (LncRNAs) in breast cancer subtypes mainly triple negativebreast cancer (TNBC) which is the most challenging category. We performed loss- and gain-offunctionexperiments and evaluated the LncRNAs roles in regulating cancer cell characteristics.Results: Our result shows that ncRNAs such as MALAT۱, PDCD۴-AS۱ and TP۵۳TG۱ playregulatory roles in breast cancer progression. In particular, our data shows TP۵۳TG۱ is acytoplasmic, relatively abundant and poly-adenyaletd transcript which plays a tumor suppressiverole in breast cancer. Upon loss-of-function experiments, we observed increased metastaticproperties in breast cancer cell lines. We studied the TP۵۳TG۱ level and its effect on survival inbreast cancer patients in The Cancer Genome Atlas (TCGA) patient database. TP۵۳TG۱ lowerlevel correlated with poor survival in breast cancer patients. We further studied the TP۵۳TG۱roles in regulation of cis- and trans-genes including CROT and UBE۲V۱.Conclusion: Breast cancer is categorized in different subtypes such as Luminal A/B, HER۲+ and triple negative (TNBC). Among all subtypes, TNBC patients show the worst prognosis.Here, we studied LncRNA players in breast cancer and proposed some molecular markers withpotential applications in TNBC patients.

کلیدواژه ها:

LncRNA ، Breast cancer ، TP۵۳TG۱ ، Tumor suppressor ، TCGA