Mir-34: A New Weapon Against Cancer?

Abstract

The microRNA(miRNA)-34a is a key regulator of tumor suppression. It controls the expression of a plethora of target proteins involved in cell cycle, differentiation and apoptosis, and antagonizes processes that are necessary for basic cancer cell viability as well as cancer stemness, metastasis, and chemoresistance. In this review, we focus on the molecular mechanisms of miR-34a-mediated tumor suppression, giving emphasis on the main miR-34a targets, as well as on the principal regulators involved in the modulation of this miRNA. Moreover, we shed light on the miR-34a role in modulating responsiveness to chemotherapy and on the phytonutrients-mediated regulation of miR-34a expression and activity in cancer cells. Given the broad anti-oncogenic activity of miR-34a, we also discuss the substantial benefits of a new therapeutic concept based on nanotechnology delivery of miRNA mimics. In fact, the replacement of oncosuppressor miRNAs provides an effective strategy against tumor heterogeneity and the selective RNA-based delivery systems seems to be an excellent platform for a safe and effective targeting of the tumor.

miRNA-34a enhances the sensitivity of gastric cancer cells to treatment with paclitaxel by targeting E2F5

“…Dysregulation and dysfunction of miRNAs leads to the initiation and development of cancers, indicating that miRNAs are important molecules that can potentially be used for the diagnosis and treatment of cancers (22). miRNA-34a has previously been identified to be frequently aberrantly expressed in human cancer, and involved in the regulation of cancer cells as a tumor suppressor (13). A previous Figure 2.…”

“…Therefore, miRNAs may serve as potential biomarkers and targets for the diagnosis and treatment of various types of cancer (12). miRNA-34a is an important regulator of tumor suppression, and acts by controlling cellular proliferation, cellular differentiation and the survival of cancer cells (13). A previous study demonstrated that the expression of miRNA-34a in GC was markedly downregulated, and that miRNA-34a was able to significantly inhibit epidermal growth factor receptor (EGFR)-signaling-dependent matrix metalloproteinase-7 (MMP-7) activation, which suggested that miRNA-34a may serve as a tumor suppresser to inhibit the cellular proliferation, migration and invasion of GC cells (14).…”

Epigenetic regulation by DNA methylation and miRNA molecules in cancer

“…MiR-34a can act as a tumor-suppressor by regulating processes such as the cell cycle differentiation, apoptosis, cancer cell viability, metastasis and chemoresistance. miR-34a might also have a benefit of a new therapeutic concept based on replacement of this miRNA expression and delivery of miRNA mimics through nanotechnology into cancer tissues without side effects on normal tissues [20].…”

“…Overall performance might be improved by combination of biomarkers within different molecular classes including cell-free DNA/ RNA, DNA methylation and many other [25]. Another described function of miRNAs is that they may act similar to hormones after being released from donor cells and are delivered from body fluids into receptor cells located in other areas [20]. However, a study analyzing circulating miRNAs from blood samples of healthy people argues against the hormone-like impact on target tissue, mainly due to extremely low concentration of circulating miRNAs when compared with plasma concentration of steroid hormones.…”

RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions

“…103 Since then, several studies have demonstrated that miR-34 is an important regulator S53 of multiple oncogenes involved in cell cycle control, cell proliferation, apoptosis, and metastasis and, consistent with a function role in cancer, its expression is deregulated in many cancer cells. 116 These data suggested that miR-34 mimics might be an attractive therapeutic strategy to restore the normal regulation of a range of cell death and survival genes in cancer cells. Consistent with this hypothesis, the mir-34 mimic MRX34, a lipid-formulated miR-34 mimic, has demonstrated efficacy in several preclinical models of cancer.…”