MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a variable incidence among different countries. Occupational asbestos exposure is the most important etiological factor and a very long latency period is widely reported. In the early phase of the disease, clinical signs are absent or not specific. For this reason, the diagnosis is frequently achieved only in the advanced stages. The histopathological diagnosis per se is also very complex, and no known factor can predict the prognosis with certainty. Nonetheless, current survival rates remain very low, despite the use of standard treatments, which include surgery, chemotherapy and radiotherapy. The identification of new prognostic and/or diagnostic biomarkers, and the discovery of therapeutic targets is a priority and could lead to a real significant impact on the management of malignant pleural mesothelioma. In this scenario, the role of microRNAs is becoming increasingly relevant, with the promise of a quick translation in the current clinical practice. Despite the relative novelty of this field, the number of works and candidate microRNAs that are present in literature is striking. Unfortunately, to date the microRNAs with the most clinical relevance for MPM are still matter of debate, probably due to the variety of approaches, techniques, and collected samples. Although specific microRNAs (e.g., let-7, miR-15 and miR-16, miR-21, miR-34a, and the miR-200 family) have been reported several times from different groups, the heterogeneity of published data reinforces the need of more comprehensive and unified studies on this topic. In this review we collect and discuss the studies focused on the involvement of microRNAs in different aspects of MPM, from their biological role in tumorigenesis and progression, to their possible application as diagnostic, prognostic and predictive biomarkers. Lastly, we examine their potential value as for the design of therapeutic approaches that could benefit MPM patients.

Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6

“…In recent years, numerous studies have demonstrated that microRNAs (miRNAs/miRs) contribute to the genesis and development of tumors (7)(8)(9). miRNAs are a group of single-stranded, noncoding RNAs ranging from 19 to 23 nucleotides in length (10).…”

P53-regulated miR-320a targets PDL1 and is downregulated in malignant mesothelioma

“…MicroRNAs (miRNAs) have a key role in regulating gene expression, underlying most biological processes 12 . Many studies focused on identifying miRNA function in cancer, evaluating the possible use of specific miRNAs, or miRNA signatures, as diagnostic, prognostic, or predictive factors in tumors, including MPM (extensively reviewed recently 13 – 17 ). Here, we performed a microarray screening to identify miRNAs that are differentially expressed between normal mesothelium and MPM of the three main histotypes with the aim of exploring the contribution of specific miRNAs to mesothelial tumorigenesis, possibly identifying new disease biomarkers and potential therapeutic targets.…”

Overexpression of miR‐199/214 is a distinctive feature of iron‐induced and asbestos‐induced sarcomatoid mesothelioma in rats

“…In lung cancer, neuroendocrine features, which are associated with an aggressive clinical course, were linked with miR‐375, 15 indicating a relationship between histopathology and miR expression. In MM, the expression profile and prognostic and diagnostic significance of miR have been reported; however, the significance of miR was not concordant, most likely due to the variety of approaches, techniques and collected samples 16,17 . In this study, we identified high expression of miR‐199/214 in SM with an miR microarray.…”