Recently Welch et al. reported that microRNA (miRNA)‐34a functions as a potential tumor suppressor in neuroblastoma cells (Oncogene 26: 5017–22, 2007). Here, we conversely show that miRNA‐34a supports cell proliferation in rat oxidative stress‐induced renal carcinogenesis and is overexpressed in various types of human cancers. While searching for genetically unstable chromosomal areas in rat renal carcinogenesis, we found the miRNA‐34 family reciprocally overexpressed in chromosomal areas with frequent allelic loss. By in situ hybridization and reverse transcription‐polymerase chain reaction, cerebral neurons and Purkinje cells showed the highest expression of a major type, miRNA‐34a, followed by a variety of endocrine cells and proliferating cells including germinal center lymphocytes and mouse embryonic fibroblasts and stem cells. In contrast, normal renal tubules, hepatocytes and myocardial cells showed faint expression. After 3 weeks of ferric nitrilotriacetate (Fe‐NTA)‐induced oxidative stress, regenerating renal proximal tubular cells showed high miRNA‐34a expression. All of the Fe‐NTA‐induced rat renal carcinomas and an array of human cancers (151 positive cases of 177) showed high expression of miRNA‐34a. Furthermore, knockdown of miRNA‐34a with small interfering RNA significantly suppressed proliferation not only of renal carcinoma cells but also of HeLa and MCF7 cells. These results indicate that miRNA‐34a overexpression, an acquired trait during carcinogenesis, supports cell proliferation in the majority of cancers suggesting an unexpected link in the cellular metabolism between cancer and neuronal and/or endocrine cells, which warrants further investigation. (Cancer Sci 2007; 98: 1845–1852)

5‐Aminolevulinic acid (ALA) is a heme precursor, pathological accumulation of which is associated with liver cancer. We show that the reactive oxygen species produced upon ALA metal‐catalyzed oxidation promote the formation of several radical‐induced base degradation products in isolated DNA. The distribution of modified bases is similar to that obtained upon gamma irradiation. This observation strongly suggests the involvement of hydroxyl radicals in the ALA‐mediated DNA damage. Increased levels of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine and 5‐hydroxy‐2′‐deoxycytidine in organ DNA of rats chronically treated with ALA were observed. This is strongly suggestive of the implication of hydroxyl radicals in the ALA‐induced degradation of cellular DNA.