Examination of the effect of Vitamin D3 on long non-coding RNA (lncRNA) expression in multiple myeloma cells

Multiple myeloma (MM) is a hematologic malignancy that develops due to the excessive proliferation of abnormal plasma cells in the bone marrow. MM, which constitutes 10% of hematological cancers, is generally seen in individuals aged 69 and above. Despite the administration of combined drug therapy and stem cell transplantation in eligible individuals, the development of drug resistance over time leads to disease relapse and patient mortality. Therefore, elucidating the molecular mechanisms involved in the development of MM is of utmost importance for early diagnosis, the development of preventive medical approaches, and overcoming drug resistance. MM arises as a result of both genetic and epigenetic abnormalities. Abnormal expression of long non-coding RNAs (lncRNAs), which are part of the epigenetic mechanism, is frequently observed in MM and in many other pathologies. Abnormal expression of lncRNAs, which may have tumor suppressor or oncogenic characteristics, promotes tumor development and drug resistance in MM. Vitamin D, known for its regulatory role in lncRNA expression, is a bone marrow microenvironmental factor and is deficient in 44% of the MM patients. Insufficient amounts of vitamin D, which can direct the transcription of lncRNAs with vitamin D response sequences (VDRE) in their promoter, may lead to dysregulation in the lncRNA expression. In this context, this thesis investigates the effect of single, or combined use of vitamin D with a proteasome inhibitor, carfilzomib, for 24 and 48 hours, on the levels of target lncRNAs (H19, NEAT1, MEG3, TUG1, UCA1) in the human MM cell line NCI-H929. According to the findings of this study, vitamin D increases the expression of the lncRNA UCA1, while it does not cause significant changes in the levels of other lncRNAs. A significant increase in UCA1 expression was also detected with the combined application of vitamin D and carfilzomib. In conclusion, vitamin D increases the transcript levels of the oncogenic lncRNA UCA1 in NCI-H929 cells. Further studies investigating the mechanism of this effect and its impact on MM cell functions are crucial for ensuring the safe use of vitamin D in MM patients.