MicroRNAs (miRNAs) are a group of small non-coding RNAs consisting of 18~24 nucleotides in length. Each miRNA is expected to bind a few hundreds of putative target mRNAs, thus inhibiting their translation into protein products mostly by degradation of targets. With its biogenesis extensively deciphered, miRNAs have been implicated in a variety of biological processes, including early development and cellular metabolism. In addition, dysregulation of miRNAs and subsequent alterations in the expression of its target molecules are thought to be linked to the pathophysiology of multiple human illnesses, including cancer. To establish the miRNA-target relationships important for developing a specific disease, it is critical to validate the putative targets of each miRNA suggested by computational methods in vivo. In this review, we will first discuss oncogenic and tumor-suppressive roles of miRNAs in human cancer and introduce computational methods to predict putative targets of miRNAs. Then, the value of Drosophila melanogaster as an alternative model system will be further discussed in studying human cancer and in validating the miRNA-target relationships in vivo. Finally, we will present a possibility of applying the mammals-to-Drosophila-to-mammals approach to study the roles of miRNAs and their targets in the pathophysiology of oral cancer, an intractable type of cancer with poor prognosis and survival rate.

Active calcium transport is carried out by calcium channel proteins, cytosolic buffering or transfer proteins, and pump proteins. Several components of this transport system have recently been determined using gene knockout (KO) models. The calbindin‐ D9k/28k and calbindin‐D9k/TRPV6 double KO mice were generated and reported that induction of expression of some duodenal calcium transport proteins can compensate for the CaBP‐9k gene deficiency. In CaBP‐9k KO mice, the levels of these hormones differ between the KO and wild‐type (WT) mice. The induction of TRPV6 in the duodenum was observed in adult KO male mice but induction was not modified by physiologic doses of 1,25(OH)2D3 and compensatory gene induction was not affected by PTH. Duodenal TRPV6 transcription in WT and female KO mice were modulated by 1,25(OH)2D3 in a dose‐dependent manner. Under calcium‐deficient dietary conditions, in DKO mice, serum calcium levels and bone length were decreased. The intestinal and renal expression of TRPV6 mRNA was significantly decreased in DKO mice fed a calcium‐deficient diet as compared to CaBP‐28k KO or WT mice, and DKO mice died after 4 weeks on a calcium‐deficient diet. Body weight, bone mineral density (BMD) and bone length were significantly reduced in all mice fed a calcium and 1,25‐(OH) D3‐ eficient diet, as compared to a normal diet, and none of the mice survived more than 4 weeks. Using microarray analysis, NCKX3 was identified as a gene that was differentially expressed in the kidneys of female and male mice. Although any hormones did not alter NCKX3 expression, however, aldosterone and hydrocortisone did down‐regulate renal NCKX3 expression in female mice. Taken together, these results indicate that deletions of CaBP‐9k and 28k has a significant effect on calcium processing under calcium‐deficient conditions, confirming the importance of dietary calcium and 1,25‐(OH)2D3 during growth and development