The seminal study by Johnson
et al. identified the
let-
7 family of miRNAs as the first tumor-suppressive miRNA known to target and regulate
KRAS[
4]. Subsequently, other tumor-suppressive miRNAs, including miR-96, miR-30c and miR-181a, have shown to regulate
KRAS in various cancers [
5]-[
7]. More recently, Gastaldi
et al. have utilized a large scale profiling technology, small RNA sequencing, to profile miRNAs in cutaneous squamous cell carcinomas (cSCCs) and identified the miR-193b/365a cluster as one of the most prominently down-regulated miRNAs in murine skin tumor progression [
8]. Their role as a tumor suppressor was confirmed in both mouse and human epidermis, as these two miRNAs modulated cellular proliferation, migration and clonogenic potential. Functional assays that showed an inverse relationship between the miRNAs and KRAS protein levels validated that the two miRNAs functioned through targeting
KRAS. Additionally, the effects of the miRNAs were recapitulated with
KRAS knockdown in squamous carcinoma cells [
8].
While several miRNA expression profiles report deregulation of numerous miRNAs in various cancers, only a few miRNAs have been characterized. Liao
et al. further investigated the role of miR-30b, one of the known down-regulated miRNAs in colorectal cancer (CRC) [
9]. The clinical relevance of miR-30b was shown in a cohort of 91 CRC cases, in which the level of miR-30b was correlated with poor progression and survival. Ectopic expression and inhibition of miR-30b affected cellular proliferation in CRC cell lines and tumor growth in a xenograft mouse model as miR-30b promotes G1 cell-cycle arrest and apoptosis. The effect of miR-30b in tumor growth was mediated through targeting many genes including
KRAS[
9].