The High Expression of the microRNA 17–92 Cluster and its Paralogs, and the Downregulation of the Target Gene PTEN, Is Associated with Primary Cutaneous B-Cell Lymphoma Progression

Abstract

The oncogenic microRNA (miR) 17-92 cluster has a causative role in the lymphomagenesis of nodal B-cell lymphomas, by activating proliferation and inhibiting apoptosis. Here we analyzed primary cutaneous B-cell lymphomas for the miR-17-92 cluster and its paralogs miR-106a-363 and miR-106b-25. In 22 primary cutaneous diffuse large B-cell lymphomas, leg type (PCLBCL-LT) compared with 22 primary cutaneous follicle center lymphomas (PCFCLs), we found that miR-20a and miR-106a were overexpressed. Multivariate Cox analysis showed that higher miR-20a and miR-20b expression levels were associated with shorter disease-free and overall survival, independently from histological type. Gene expression profiling also showed a downregulation of 8 candidate target genes of miR-20a, miR-20b, and miR-106a in PCLBCL-LT compared with PCFCL. Among the candidate target genes, PTEN, NCOA3, and CAPRIN2 were confirmed to be underexpressed in PCLBCL-LT using quantitative reverse transcriptase-PCR on CD20-positive laser-microdissected tumor cells. In multivariate Cox analysis, lower PTEN mRNA expression level was associated with shorter disease-free survival (DFS), independently from the histological type. Altogether, this molecular and bioinformatic study of 44 patient skin biopsy samples showed that the oncogenic miR-17-92 cluster and its paralogs were involved in cutaneous B-cell lymphoma progression, and that the downregulation of the target gene PTEN was associated with shorter DFS.

Therapeutic strategy with artificially-designed i-lncRNA targeting multiple oncogenic microRNAs exhibits effective antitumor activity in diffuse large B-cell lymphoma

“…Based on the mechanism of miRNA function, the OncomiRs can target a varity of onco-suppressor genes and inhibit their post-transcriptional expression. For example, PTEN (phosphate and tensin homolog) is a tumor suppressor gene, which was regulated by several miRNAs, such as miR-21 [12], miR-155 [13], miR-221/222 [14], and miR-17~92 cluster [15]. In DLBCL, the high-expressed OncomiRs bind to PTEN mRNA and inhibit its expression.…”

Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages

“…22,25,27,28 However, there has been limited research to define the underlying mechanism. The Bim gene expression was inversely associated with miR-20a-5p, suggesting it could be a target gene of miR20a-5p.…”

“…20 This cluster is frequently overexpressed in human cancers and has been shown to promote several aspects of oncogenic transformation, including proliferation and evasion of apoptosis. 21,22 Among the members of miR-17 family, miR-20a has been extensively studied on its role in tumor development and progression. It was reported that miR-20a was up-regulated in anaplastic thyroid cancer, 23 and it could promote gastric cancer cell proliferation and inhibit cell apoptosis via post-transcriptional modulation of p21 and TP53INP1.…”

miR-20b Inhibits T Cell Proliferation and Activation via NFAT Signaling Pathway in Thymoma-Associated Myasthenia Gravis

“…miR-20b also regulates the expression of the proteinase-activated receptor-1 (PAR-1) thrombin receptor in melanoma cells [12]. It has been demonstrated to regulate several cancers, including gastric [13], liver [14], cervical [15], colon [16], lung [17], and lymphoma [18]. However miR-20b's function in thymoma development and implications of thymoma in myasthenia gravis pathophysiology have not been previously systematically investigated.…”