Open AccessAssociation of microRNA‐34a overexpression with proliferation is cell type‐dependent
Author(s) -
Dutta Khokon Kumar,
Zhong Yi,
Liu YuTing,
Yamada Takuji,
Akatsuka Shinya,
Hu Qian,
Yoshihara Minako,
Ohara Hiroki,
Takehashi Masanori,
Shinohara Takashi,
Masutani Hiroshi,
Onuki Janice,
Toyokuni Shinya
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00619.x
Subject(s) - carcinogenesis , biology , microrna , cell growth , cancer research , gene knockdown , oncogene , cancer cell , cell , microbiology and biotechnology , cancer , cell culture , gene , genetics , cell cycle
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)