Abstract 976: Long non-coding RNA Fendrr as biomarker for lung cancer
Authors: Herrera-Merchan Antonio , Cuadros Marta , Rodriguez Sandra , Torres Raul , Farez Esther , Medina Pedro 
Published: July 2016

Background. Carcinogenesis has been extensively studied at a molecular level however, only since some years ago this research field has been fed by the discovery of a new type of long non-coding RNAs that are able to regulate gene expression and control various cellular mechanisms: Long non-coding RNA (LncRNA). In this study we have focused on the LncRNA Fendrr, which is located on chromosome 16 (16q24.1). This gene produces a long non-coding RNA transcribed bidirectionally with the Forkhead box-F1 (Foxf1) transcription factor on the opposite strand. The distance between Fendrr and FoxF1 is around 1700 bp and it seems to contain the promoter of both genes. In addition, the function of LncRNA Fendrr is currently unknown.

There is controversial data about the possible correlation between Fendrr and FoxF1. Szafranski et al (Genome Res. 2013) showed that Fendrr downregulates FoxF1 (by using siRNA against Fendrr). On the other hand, Cabili et al (Genome Biol. 2015) demonstrated that the mRNA of Fendrr and Foxf1 are in the same proportion and localization (nucleus and cytoplasm) and Grote et al (RNA Biol. 2013) indicated that Fendrr interacts with PRC2 complex, which is able to inhibit FoxF1 expression. However, Xu et al (J Hematol Oncol. 2014) showed that, regardless of an overexpression or knockdown of Fenderr, any change in FoxF1 expression was found.

Objective. One of the principal aims of this study is to investigate how Fendrr and FoxF1 are silenced in lung cancer and which are their functions.

Results. Our preliminary results show that 17 out of 20 (85%) human lung cancer cell lines tested, didn′t express neither Fendrr nor Foxf1. However, to date, it has not been identified any mutation in Fendrr or FoxF1 in these cell lines.

In addition, it has been seen that methylation of the promoter and the response of 5-aza is dependent of the p53 status. Moreover, we have observed that ectopic overexpression of LncRNA Fendrr increases the expression of FoxF1 in some lung cancer cell lines and, interestingly, inhibition of FoxF1 gene increases expression of Fendrr. In contrast, inhibition of Fendrr does not seem to produce any change in FoxF1 expression. This could mean that Fendrr regulates FoxF1 expression but requires the help of other components.

Our main goal is to investigate whether Fendrr and FoxF1 are silenced in lung cancer cell lines and how demethylating agents can re-express Foxf1 and Fendrr genes. In addition, we will explore the epigenetic patterns of lncRNAs in lung cancer cell lines using sequencing-based methylome data.

Conclusion. We demonstrate that Fendrr and FoxF1 are silenced by methylation in p53 mutated human lung cancer cells lines and we also have observed that Fendrr regulates the expression of FoxF1. All there results could support the hypothesis the role of Fendrr in regulating FoxF1 expression, a gene that could be a putative tumor suppressor.

Citation Format: Antonio Herrera-Merchan, Marta Cuadros, Sandra Rodriguez, Raul Torres, Esther Farez, Pedro Medina. Long non-coding RNA Fendrr as biomarker for lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 976.