Down-regulation of MEG3, PANDA and CASC2 as p53-related lncRNAs in breast cancer

Article type: Research Article

Authors: Ghafouri-Fard, Soudeh^a | Sohrabi, Behnoush^b | Hussen, Bashdar Mahmud^c | Mehravaran, Elham^d | Jamali, Elena^e | Arsang-Jang, Shahram^f | Fathi, Mohadeseh^g | Taheri, Mohammad^h; | Samsami, Majid^i;

Affiliations: [a] Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [b] Department of Biology, Faculty of Sciences, Arak University, Arak, Iran | [c] Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Kurdistan Region, Iraq | [d] Motamed Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran | [e] Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [f] Cancer Gene Therapy Research Center, Zanjan University of Medical Science, Zanjan, Iran | [g] Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [h] Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [i] Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Correspondence: [*] Corresponding authors: Mohammad Taheri, Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. E-mail: [email protected]. Majid Samsami, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. E-mail: [email protected]

Abstract: TP53 encodes a major tumor suppressor protein which blocks carcinogenesis process in a variety of tissues including breast tissue. Expression and function of this gene is regulated by a number of long non-coding RNAs (lncRNAs) among them are PANDA, MEG3 and CASC2. We measured expression of TP53 and these transcripts in a cohort of Iranian breast cancer patients. Expression levels of TP53, MEG3, CASC2 and PANDA were significantly lower in tumoral samples compared with non-tumoral samples (Posterior mean differences =  −4.26, −1.66, −5.98 and −3.13, respectively; P values < 0.0001). Expression of CASC2 was higher in Her2 1+ cases compared with Her2 negative cases (Beta = 1.85, P value = 0.037). Expression levels of MEG3 and TP53 were lower in grade 2 samples compared with grade 1 (Beta = −1.86, P value = 0.006 and Beta = −2.24, P value = 0.003, respectively). There was no other significant association between expression of genes and clinical variables. CASC2 had the best performance among these genes with area under curve value of 0.78 and sensitivity and specificity values of 56.33% and 88.73%, respectively (P value < 0.0001). The current investigation supports the role of TP53-related lncRNAs in the pathogenesis of breast cancer.

Keywords: TP53, lncRNA, PANDA , MEG3 , CASC2

DOI: 10.3233/BD-210069

Journal: Breast Disease, vol. 41, no. 1, pp. 137-143, 2022