Analysis of Mir-7 (microRNA-7) Expression in Non-Hodgkin Lymphomas and Its Possible Role in the Regulation of the Transcription Factor KLF4 and YY1

Previous report has been shown that microRNA-7 (miR-7) play a important role in the development of various types of cancer such as lung, hepatocellular, breast, among others, however, in Non-Hodgkin's Lymphoma (NHL) the role of miR-7 has not been studied. On the other hand, studies carried out by several groups report miR-7 as a direct regulator of the expression of KLF4 and YY1, both proteins function as transcription factors and have been reported by our group as important factors for development of malignancy in lymphoma (Valencia-Hipolito 2014). The objective of this work was to determine the possible correlation between miR-7-KLF4-YY1 in vitro as well as in clinical samples of lymphoma patient. Expression of KLF4 and YY1 were analyzed in several B-NHL cell lines by western blot, in addition KLF4, YY1 and miR-7 was analyzed by real-time PCR in LNH cell lines (Ramos, Raji, DHL4). The expression of KLF4 and YY1 was correlated with miR-7 expression in B-NHL cell lines. A tissue microarray (TMA) was constructed with 36 biopsies of NHL patients. TMA were analyzed by mIR-7 expression for hybridization in situ, as well as the expression of KLF4 and YY1 by immunohistochemistry. Finally, miR-7 expression was correlated with YY1 and KLF4 in TMA tissues. Our results shown an inverse correlation of miR-7 expression with KLF4 and YY1 expression on B-NHL cell lines. Also, miR-7 expression correlates inversely with the expression of KLF4 and YY1 in TMA of NHL samples, our results evidenced in the cell lines at both the messenger RNA and protein levels confirming the previously observed pattern in the TMA. Recent results in our laboratory suggest that YY1 regulates the expression of KLF4 in NHL (Vega et al 2013) however the mechanism by which YY1 is regulated in NHL has not been studied. Our results suggest that miR-7 can regulate the expression of both YY1 and KLF4 or the expression of YY1 and this expression of KLF4 in NHL, which could be an important prognostic marker.The results obtained suggest that miR-7 is involved in the regulation of KLF4 and YY1, both in patient biopsies and in NHL cell lines.

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Mario I Vega, et al Yin Yang 1 (YY1) Regulates The Transcription Of The Gene Krüppel-Like Factor 4 (KLF4) In Pediatric Burkitt Lymphoma: Clinical Implications Blood 2013 122:3004