Programmed cell death 4 and microRNA 21 inverse expression is maintained in cells and exosomes from ovarian serous carcinoma effusions

Abstract

Ovarian serous carcinoma (OSC) is a fatal gynecologic malignancy usually presenting with bilateral localization and malignant peritoneal effusion. Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is directly controlled by microRNA-21 (miR-21). Exosomes are small cell-derived vesicles that participate in intercellular communication, delivering their cargo of molecules to specific cells. Exosomes are involved in several physiological and pathological processes including oncogenesis, immunomodulation, angiogenesis, and metastasis. The current study analyzed the expression of PDCD4 and miR-21 in resected OSC specimens and in cells and exosomes from OSC peritoneal effusions. PDCD4 was immunohistochemically examined in 14 normal ovaries, 14 serous cystadenoma (CA), and 14 OSC cases. Quantitative reverse transcriptase-polymerase chain reaction analysis of PDCD4 and miR-21 expression was performed in CA and OSC cases and in cells and exosomes obtained from 10 OSC and 10 nonneoplastic peritoneal effusions. miR-21 was also evaluated by in situ hybridization. Immunohistochemistry demonstrated a gradual PDCD4 loss from normal ovaries to CA and OSC specimens. Quantitative reverse transcriptase-polymerase chain reaction displayed higher PDCD4 messenger RNA levels in CA specimens compared with OSC cases and highlighted miR-21 overexpression in OSC specimens. In situ hybridization detected miR-21 only in OSC cells. This PDCD4 and miR-21 inverse expression was also noted in cells and exosomes from OSC peritoneal effusions compared with nonneoplastic effusions. PDCD4 and miR-21 are involved in OSC oncogenesis. The transfer of miR-21 by exosomes could promote oncogenic transformation in target cells distant from the primary tumor without direct colonization by cancer cells and could be used as a diagnostic tool

Significance of microRNA 21 in gastric cancer

“…microRNA 21, also known as hsamir-21 or miRNA 21 is encoded by the miR-21 gene located on chromosome 17q23.2 immediately downstream of the vacuole membrane protein-1 (VMP1) gene [4,6]. miR-21 is a common microRNA that is upregulated in a wide variety of cancers, including breast [13] ovaries [14] cervix [15] colon [16] lung [17] and liver [18]. In addition, it has been identified that miR-21 is consistently upregulated in several types of human cancers, including the stomach, as compared with matching non-cancerous tissue [19].miR-21 is also an oncogenic miRNA that can modulate the expression of multiple tumour suppressor genes, such as phosphatase and tensin homolog (PTEN), Serpini1, and programmed cell death 4 protein (PDCD4) [20,21].…”

miR-19a and SOCS-1 expression in the differential diagnosis of laryngeal (glottic) verrucous squamous cell carcinoma

“…Since there was a risk of consuming the whole of the specimen available, no further sections were obtained in two cases (one VSCC and one conventional SCC) to comply with the institute's ethical regulations on research conducted on human tissues. Staining was done automatically (BondmaX, Menarini, Florence, Italy) as described elsewhere,22 23 using the Bond Polymer Refine Detection kit (Leica Microsystem, Wetzlar, Germany), with rabbit polyclonal anti-SOCS-1 antibody (Santa Cruz Biotechnology, Santa Cruz, California, USA; working dilution 1:20, citrate buffer). Sections were then slightly counterstained with haematoxylin.…”

MicroRNAs in Ovarian Cancer

“…The demonstrated association between miRNA and their targets has most frequently been negative [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55], as summarized in Table 2. Notably, the association between miRNAs and their targets is not always straightforward, which is demonstrated by the little overlap between predicted and experimentally shown targets [56].…”