Role of Metastasis-Related microRNAs in Prostate Cancer Progression and Treatment

Abstract

Prostate cancer (PCa) is one of the most prevalent cancer types in males and the consequences of its distant metastatic deposits are the leading cause of PCa mortality. Therefore, identifying the causes and molecular mechanisms of hematogenous metastasis formation is of considerable clinical importance for the future development of improved therapeutic approaches. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level by targeting messenger RNAs. Numerous studies have identified miRNAs as promotors or inhibitors of metastasis and revealed, in part, their targeting pathways in PCa. Because miRNAs are remarkably stable and can be detected in both tissue and body fluid, its potential as specific biomarkers for metastasis and therapeutic response is also currently under preclinical evaluation. In the present review, we focus on miRNAs that are supposed to initiate or suppress metastasis by targeting several key mRNAs in PCa. Metastasis-suppressing miRNAs include miR-33a-5p, miR-34, miR-132 and miR-212, miR-145, the miR-200 family (incl. miR-141-3p), miR-204-5p, miR-532-3p, miR-335, miR-543, miR-505-3p, miR 19a 3p, miR-802, miR-940, and miR-3622a. Metastasis-promoting RNAs, such as miR-9, miR-181a, miR-210-3, miR-454, miR-671-5p, have been shown to increase the metastatic potential of PCa cells. Other metastasis-related miRNAs with conflicting reports in the literature are also discussed (miR-21 and miR-186). Finally, we summarize the recent developments of miRNA-based therapeutic approaches, as well as current limitations in PCa. Taken together, the metastasis-controlling miRNAs provide the potential to be integrated in the strategy of diagnosis, prognosis, and treatment of metastatic PCa. Nevertheless, there is still a lack of consistency between certain miRNA signatures and reproducibility, which impedes clinical implementation.

Personalized 3-Gene Panel for Prostate Cancer Target Therapy

“…Some therapies that work against the consequences of altered genes (e.g., use of olaparib for HRR gene-mutated metastatic castrationresistant prostate cancer [70,71]) were already granted FDA approval (all FDA-approved therapies for PCa are listed in Reference [72] and partially discussed in Reference [73]). Gene therapy targets not only protein-coding genes but also long non-coding RNAs [74] and microRNAs [75]. PCa FDA-approved therapies also include inhibitors of the androgen receptor signaling, such as enzalutamide [76,77] and darolutamide [78,79].…”

Advances in the Application of Exosomes Identification Using Surface-Enhanced Raman Spectroscopy for the Early Detection of Cancers

“…PD-L1 exosomes can be quantitatively labeled using PD-L1 antibody-modified Au@Ag@ MBA-SERS labeling. Mi RNA plays an important role in the post-transcriptional regulation of gene expression and plays an essential role in the diagnosis and treatment of tumors ( Li et al, 2021a ; Andrikopoulou et al, 2021 ; Crudele et al, 2021 ; Konoshenko et al, 2021 ; Oh-Hohenhorst and Lange, 2021 ). The nature of the exosomal lipid bilayer avoids miRNA degradation, making the specific miRNAs in exosomes well suited as biomarkers for early cancer diagnosis and prognosis.…”

MetastamiRs: The Role of MicroRNAs in the Metastatic Phenotype of Prostate Cancer

“…Due to a multitude of treatment options that often offer curative potential, localized disease generally portends favorable outcomes, with 5-year survival for localized and regional disease being nearly 100% (17). However, despite noteworthy recent progress in therapeutic measures, metastatic prostate cancer still inflicts significant morbidity and mortality, with the preponderance of fatal cases of prostate cancer attributed to metastatic burden (18)(19)(20).…”

“…Whereas some of these metastasis-promoting miRNAs directly activate oncogenic pathways via known proto-oncogenes, others silence or suppress tumor-suppressive pathways to promote prostate cancer metastasis. For example, Ren et al demonstrated that miR-210-3p sustains the activation of nuclear factor kappa -B (NF-κB) signaling by targeting tumor necrosis factor-α (TNFα), which increases the capacity for cellular invasion, migration, EMT, and formation of bone metastases (19,30). On the other hand, Yu et al…”