These findings, together with the fact that miR-34 is down-regulated in several types of human cancer, show that miRNAs can affect tumorigenesis by working within the confines of well-known tumor suppressor pathways.
Aberrantly increased expression of miR-21 plays a significant role in lung carcinogenesis and is a potential therapeutic target in both epidermal growth factor receptor-mutant and wild-type cases. miR-34 may be necessary for the radiation-induced DNA damage response.
This circuitry mechanism for p53 activation is of interest in understanding the tumor suppressive function of miR-34a in colon carcinogenesis. miRNA should also be considered as novel anti-cancer agents in tumor suppressive therapeutic applications.
Our preliminary study suggests that miR-34a, although having a role in late tumorigenesis, does not contribute to the inherited susceptibility to cutaneous melanoma.
Furthermore, in contrast to p53-deficient mice, miR-34-deficient animals do not display increased susceptibility to spontaneous, irradiation-induced, or c-Myc-initiated tumorigenesis.
The critical role of miR-34a in p53-mediated cell cycle arrest and apoptosis invokes studies focusing on the specific role of miR-34a dysregulation in carcinogenesis.
Aberrant expression of microRNA-34a (miR-34a) has been reported to be involved in the tumorigenesis and progression of various classes of malignancies.
Numerous studies have focused on the association between miR-34 family members, which are direct p53 targets, and carcinogenesis of many cancers, including hepatocellular carcinoma (HCC).
Recently, microRNAs (miRNAs) including miR-34 family have been found to play a critical role in tumorigenesis through regulating the expression of its target genes, which are involved in many cellular processes such as cell proliferation, survival, apoptosis, migration, invasion and angiogenesis.
Previous studies have focused on the association of miR-34 family members with carcinogenesis of many cancers, including hepatocellular carcinoma (HCC).
However, it has been reported that while GAS1 is down-regulated in papillary thyroid carcinoma (PTC), miR-34a is up-regulated in this specific type of cancer, although their potential roles in PTC tumorigenesis have not been examined to date.
The p53:miR-34a:E2F positive feed-forward loop and the p53:miR-605:Mdm2 positive feed-back loop have been identified to be crucial oncogenesis/tumor suppressor-regulating signaling pathways.
In this review we describe the potential role of miR-125b and miR-34a in cervical carcinogenesis, including interaction with HPV and mechanism of deregulation.
However, miR-34a deficiency strongly promotes tumorigenesis when p53 is haploinsufficient, suggesting that the defective p53-miR-34 feedback loop can enhance oncogenesis in a specific context.