*5.1.4 miR-34*

miR-34 is one of the most important TS-miRs, being positively controlled by TP53 [57], repressed by MYC [58], and silenced by aberrant CpG methylation [59].

Overexpression of miR-34 was related to apoptosis and cell cycle arrest [60], while its underexpression was linked to different tumor types, including nonsmall-cell lung cancer (NSCLC) [61], breast cancer [62], or ovarian cancer [63]. Several studies have proved that ionizing radiation upregulates the levels of expression from different miR-34 family members in a variety of human cell types: miR-34b in lymphocytes [64], miR-34c in prostate cancer cell lines [65], and miR-34a in thyroid cells [66]. Consequently, to increase the therapeutic efficiency, some of the future studies should focus on the combined use of DNA damage response related to miRNAs and radio- or chemotherapy. By performing a miR-34 modulation, Trang et al. [47] have demonstrated that synthetic miR-34 mimics incorporated in a lipid-based particle was able to block tumor growth in a mouse model of nonsmall cell lung. Likewise, Daige et al. [67] have proved that the use of encapsulating miR-34a mimics into liposomes (MRX34) leads to increase the level of miR34a in liver tumors, followed by significantly reducing several of its mRNA targets, and consequently tumor regression.

Based on these results, encapsulating miR-34a mimics into liposomes (MRX34, Mirna Therapeutics Inc.) was later proposed to be investigated in clinical trials [68].
