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Mitogen-activated protein kinase (MAP kinase) pathways participate in regulation of several cellular processes involved in breast carcinogenesis. A number of non-coding RNAs including both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate or being regulated by MAPKs. We performed an  in-silico  method for identification of MAPKs with high number of interactions with miRNAs and lncRNAs. Bioinformatics approaches revealed that MAPK14 ranked first among MAPKs. Subsequently, we identified miRNAs and lncRNAs that were predicted to be associated with MAPK14. Finally, we selected four lncRNAs with higher predicted scores ( NORAD ,  HCG11 ,  ZNRD1ASP  and  TTN-AS1 ) and assessed their expression in 80 breast cancer tissues and their adjacent non-cancerous tissues (ANCTs). Expressions of  HCG11  and  ZNRD1ASP  were lower in tumoral tissues compared with ANCTs (P values < 0.0001). However, expression levels of  MAPK14  and  NORAD  were not significantly different between breast cancer tissues and ANCTs. A significant association was detected between expression of  HCG11  and estrogen receptor (ER) status in a way that tumors with up-regulation of this lncRNA were mostly ER negative (P value = 0.04). Expressions of  ZNRD1ASP  and  HCG11  were associated with menopause age and breast feeding duration respectively (P values = 0.02 and 0.04 respectively). There was a trend towards association between  ZNRD1ASP  expression and patients’ age of cancer diagnosis. Finally, we detected a trend toward association between expression of  NORAD  and history of hormone replacement therapy (P value = 0.06). Expression of  MAPK14  was significantly higher in grade 1 tumors compared with grade 2 tumors (P value = 0.02). Consequently, the current study provides evidences for association between lncRNA expressions and reproductive factors or tumor features.

In silico identification of MAPK14-related lncRNAs and assessment of their expression in breast cancer samples