MCF-7 hücrelerinde NKILA susturumunun Hsp90, NF-κB ve β-Katenin üzerindeki etkileri

Breast cancer is still a prevalent cancer type among women and has a very high mortality rate. Normally, cancer treatments rely on targeting the oncogenic proteins. However, targeted therapy success can be very low depending on the cancer cell type, cell surface markers difference, and resistance to apoptosis of the cancer cells. Recent discoveries showed that not only proteins but non-coding RNAs are also involved in signalling networks in all cancer types. LncRNAs are one type of non-coding RNA and longer than 200 bp, they are similar to the mRNAs but lack ORF in their structure accordingly does not involve codes for the protein synthesis. However, their role in the cells is so variable but most of them can interact with the proteins. NF-κB is another important transcriptional factor directly related to cancer progression and regulated by NKILA which is another lncRNA. NKILA is defined as a negative regulator of the NF-κB, and NKILA inhibition has been shown as related to poor prognosis in cancer patients. Up to date, its relation with only a few signals transducing proteins has been elucidated. Nevertheless, NKILA association with other oncogenic proteins HSP90 and βcatenin never shown before and should be enlightened to clarify the role of the transcript which may give us important clues about the cancer prognosis. NF-κB, Wnt signalling, and the HSR system might collaborate to develop cancerous progress because of the strict correlation of NFκB with the HSP90 and β-catenin. In this case, NKILA might affect the β-catenin and HSP90 expression profiles. β-catenin is a controversial protein because it can collaborate with NF-κB proteins or can be antagonistic to the NF-κB at the same time, but NF-κB is positively associated with the HSP90. Thus, we aimed to study the association of NKILA with two of these crosstalking molecules using western blot and RT-qPCR methods. Indeed, we found that NKILA inhibition resulted in to increase of NF-κB and HSP90 but a decline in β-catenin levels. We detect the NF-κB and HSP90 upregulation but decline in the β-catenin levels. Therefore, we suggest that NKILA also has a regulatory role on the HSP90 as well as NF-κB, but the decrease of β-catenin can be explained by the catenin- NF-κB cross-regulation during the cell cycle. These novel findings are important to reveal the NKILA mechanism in the cancer cell which can be a helpful therapeutical target.