**5.3. miRNAs and drug resistance**

Several miRNA, some of them related to apoptosis, have been associated with drug resistance. Deregulation of miR-214 is a recurrent event in human ovarian cancer and it has been shown that miR-214 induces cell survival and cisplatin resistance primarily through targeting the PTEN/Akt pathway [196]. Also, is known that the let-7 family of miRs plays a role in a host of cellular functions such as modulation of drug sensitivity. The miRNA let-7a which directly targeting caspase-3 is over-expressed in some human cancers and has been shown to induce resistance to a variety of drugs caspase-3-dependent apoptosis, including doxorubicin, paclitaxel and interferon-gamma. Let-7e was up-regulated in some ovarian cancer cell lines with increased resistance to doxorubicin. On other hand, it has been reported that let-7i is down-regulated in chemotherapy-resistant ovarian cancer, and reintroduction of let-7i can sensitize resistant ovarian cancer cell lines to platinum-based chemotherapy [188]. In a non small cell lung cancer cell line, the down-regulation of miR-186\* which increased the expression of its direct target, Caspase-10, has been indicated the cause of the apoptosis induced by the chemopreventive agent curcumin [189]. Thus, the effect of anti-cancer drugs that modulate cell proliferation apoptosis on miRNA expression profiles was explored and could help for predicting apoptosis resistance. As a result, the knowledge of potential miRNAs implicated in apoptosis resistance could avoid unnecessary morbidity and may represent a novel class of biomarkers for facilitating personalized treatment.
