Further investigations on prostate cancer indicated castration-resistance due to the overexpression of HOTAIR. Thus, activity of this lincRNA induces a distinct mode of androgen receptor (AR) gene regulation through interaction with MDM2 (an E3 ubiquitin ligase), prohibiting the respected protein ubiquitination and consequently AR degradation; while, overexpression of HOTAIR is sufficient to activate androgen-independent AR and promote drug-resistance in the absence of androgen, through AR-mediated transcriptional pathway [96]. Here, AR is linked to Familial prostate cancer.