microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

Abstract

As the most frequently diagnosed non-skin cancer in men and a leading cause of cancer-related death, understanding the molecular mechanisms that drive treatment resistance in prostate cancer poses a significant clinical need. Radiotherapy is one of the most widely used treatments for prostate cancer, along with surgery, hormone therapy, and chemotherapy. However, inherent radioresistance of tumor cells can reduce local control and ultimately lead to poor patient outcomes, such as recurrence, metastasis and death. The underlying mechanisms of radioresistance have not been fully elucidated, but it has been suggested that miRNAs play a critical role. miRNAs are small non-coding RNAs that regulate gene expression in every signaling pathway of the cell, with one miRNA often having multiple targets. By fine-tuning gene expression, miRNAs are important players in modulating DNA damage response, cell death, tumor aggression and the tumor microenvironment, and can ultimately affect a tumor's response to radiotherapy. Furthermore, much interest has focused on miRNAs found in biofluids and their potential utility in various clinical applications. In this review, we summarize the current knowledge on miRNA deregulation after irradiation and the associated functional outcomes, with a focus on prostate cancer. In addition, we discuss the utility of circulating miRNAs as non-invasive biomarkers to diagnose, predict response to treatment, and prognosticate patient outcomes.

Mechanisms of Taxane Resistance

“…Alterations in miRNAs/lncRNAs are associated with prostate cancer [ 413 , 414 ]. As the mechanisms behind taxane resistance in CRPC become more defined, the roles of both miRNAs and lncRNAs are emerging [ 305 , 415 , 416 , 417 , 418 ].…”

miR-541-3p enhances the radiosensitivity of prostate cancer cells by inhibiting HSP27 expression and downregulating β-catenin

“…Moreover, a considerable number of studies have demonstrated the dysregulation of multiple miRNAs in PCa, which suggests the use of miRNAs as potential biomarkers for the prediction and prognosis of the disease 4 . In addition, the expression of multiple miRNAs can be altered by radiation in PCa cells and surrounding cells, which are exposed in radiation treatment 6 , 7 . So far, several factors have been documented to be involved in the mutual effects between radiation and miRNAs: first, miRNAs could perform an inhibition role in DNA damage repair induced by radiotherapy 8 .…”

“…Several miRNAs have also been reported to exhibit upregulated expressions after radiation so as to modulate the cell cycle progression 9 , 10 . During cell death induced by radiation, miRNAs could provoke cell cycle arrest and increase the radioresistance; furthermore, miRNAs can also regulate epithelial-mesenchymal transition (EMT) 11 , which is often affected by radiation 7 , 12 .…”

Mechanisms by Which MnTE-2-PyP Suppresses Prostate Cancer Cell Growth

“…Ionizing radiation produces free radicals, which results in DNA damage and subsequently halts the fast proliferation of prostate cancer cells. Permanent cell cycle arrest or cell death will occur if DNA repair is not successful [21,22]. Though highly efficient, there are several issues with radiotherapy.…”