(624.5) Signaling Pathways Associated with miR-106b mediated Radioresistance in the Treatment of Colorectal Cancer

Poster Board Number: E663

Susana Rubio-Guevara (Universidad Nacional de Trujillo), Karyn Olascuaga-Castillo (Universidad Nacional de Trujillo), Elena Cáceres-Andonaire (Universidad Privada Antenor Orrego), Dan Altamirano-Sarmiento (Universidad Privada Antenor Orrego, Universidad Privado Antenor Orrego), Olga Caballero-Aquiño (Universidad Nacional de Trujillo), Elena Mantilla-Rodríguez (Universidad Nacional de Trujillo), Julio Hilario-Vargas (Universidad Nacional de Trujillo), Maxim Berezovski (University of Ottawa), José Andrés Morgado-Díaz (Instituto Nacional de Cancer)

Tumor radioresistance, or the lack of control of certain tumors with this treatment, can result in locoregional recurrence; therefore, there is great interest in understanding the underlying biology and developing strategies to overcome this problem. MicroRNAs (miRNAs, miRs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level and participate in cancer invasion, progression, metastasis, and therapeutic resistance. Emerging evidence indicates that miRNAs play a critical role in modulating key cellular pathways that mediate response to radiation, influencing radiosensitivity of cancer cells through interaction with other biological processes such as cell cycle checkpoints, apoptosis, autophagy, epithelialmesenchymal transition, and cancer stem cells. Today, most studies on patient data report different, results on the miRNAs evaluated for each tumor type, highlighting miR-106b whose overexpression can determine radioresistance both in vitro and in vivo by inhibiting apoptosis and promotion of cell proliferation. The objective of this study was to find the signaling pathways involved with miR-106b-mediated radioresistance.

Methods: CRC gene expression data sets were collected from the public database, The Cancer Genome Atlas (TCGA). In addition, web-based tools were used to explore TCGA data, specifically that developed by the Memorial Sloan Kettering Cancer Center (MSK) cBioPortal for Cancer Genomics. The public site cBioPortal is hosted at the MSK Molecular Oncology Center, in which the term “colorectal cancer” was searched and 12 studies were selected, creating a single combined study which has 4341 patients and 4488 samples, within which the search for miR-106b was carried out and the signaling pathways involved with the expression mediated by this miRNA were obtained.

Results: The following signaling pathways involved with miR-106b were obtained: WNT, TP53, TGF-Beta, RTK-RAS, PI3K, NRF2, NOTCH, MYC, HIPPO, and its influence on the cell cycle was also noted.

Conclusion: miRNAs have been shown to play an important role in the regulation of CRC radio resistance, by controlling various signaling pathways, including cell cycle, proliferation, apoptosis, and DNA damage repair. Furthermore, these results are consistent with recent data that have shown that selective modulation of miRNA activity can improve the response to radiotherapy, providing an innovative antitumor approach based on miRNA-related gene therapy. Therefore, miRNAs could also serve as targets for the development of new therapeutic strategies to overcome radiation resistance in CRC.

This research was funded by the Doctoral Program in Pharmacy and Biochemistry of the National University of Trujillo. Peru and the National Council of Science and Technology - Peru (CONCYTEC) in cooperation with the World Bank (Contract N 07-2018-FONDECYTBM-IADT-MU).





Vías TP53 y KRAS; Vías MYC y PIK3