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PRMT8 demonstrates variant-specific expression in cancer cells and correlates with patient survival in breast, ovarian and gastric cancer.

ABSTRACT: Recent emphasis has been placed on the role of epigenetic regulators and epigenetic marks as biomarkers for cancer diagnosis and prognosis, and as therapeutic targets for treatment. One such class of regulators is the protein arginine methyltransferase (PRMT) family. The present study examined available curated data regarding the expression and alteration of one of the least studied PRMT family members, PRMT8, in various types of cancer and cancer cell lines. Publicly available cancer data on PRMT8 expression were examined using the Human Protein Atlas and the Kaplan-Meier Plotter, and reverse transcription-polymerase chain reaction was used to screen a selection of human cell lines for variant-specific PRMT8 expression. High levels of PRMT8 expression in breast, ovarian and cervical cancer was observed. Additionally, in patients with breast and ovarian cancer, high PRMT8 expression was correlated with increased patient survival, whereas in gastric cancer, high PRMT8 expression was correlated with decreased patient survival. The present study also investigated the expression of PRMT8 variant 2, a novel transcript variant recently identified in our laboratory, in various cancer cell lines. Variant-specific expression of PRMT8 in numerous distinct cancer cell lines derived from different tissues, including the expression of the novel PRMT8 variant 2 in U87MG glioblastoma cells was demonstrated. The present study proposes the possibility of PRMT8 as a cancer biomarker, based on the high level of PRMT8 expression in various types of cancer, particularly in tissues that would not normally be expected to express PRMT8, and on the correlation of PRMT8 and patient lifespan in several cancer types. Variant-specific expression of PRMT8 in diverse cancer cell lines suggests the possibility of alternate PRMT8 isoforms to have diverse effects on cancer cell phenotypes.

SUBMITTER: Hernandez SJ

PROVIDER: S-EPMC5403539 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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PRMT8 demonstrates variant-specific expression in cancer cells and correlates with patient survival in breast, ovarian and gastric cancer.

Hernandez Sarah J SJ Dolivo David M DM Dominko Tanja T

Oncology letters 20170201 3

Recent emphasis has been placed on the role of epigenetic regulators and epigenetic marks as biomarkers for cancer diagnosis and prognosis, and as therapeutic targets for treatment. One such class of regulators is the protein arginine methyltransferase (PRMT) family. The present study examined available curated data regarding the expression and alteration of one of the least studied PRMT family members, PRMT8, in various types of cancer and cancer cell lines. Publicly available cancer data on PR ...[more]

PMID: 28454353

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Project description:The cause of death among the majority of epithelial ovarian cancer (EOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Thus, it is important to identify the factors that mediate EOC metastasis and implantation, including clearance of the mesothelium. Sushi domain containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Immunohistochemical analysis determined the presence of SUSD2 in several subtypes of EOC, with the strongest staining observed in high-grade serous ovarian carcinomas (HGSOCs). A high-density, clinically annotated HGSOC tissue microarray was stained with an anti-SUSD2 antibody. Patients with tumors that had a low percentage of SUSD2 staining cells had a shorter median survival (31.7 months) compared with patients who had tumors with extensive SUSD2 staining (49.1 months; P-value=0.0083). To investigate the role of SUSD2 in HGSOCs, stable OVCAR3, OVSAHO and KURAMOCHI cell lines were established with knockdown (KD) or non-targeting (NT) of SUSD2. Boyden chamber and wound-healing assays demonstrated that OVCAR3, OVSAHO and KURAMOCHI SUSD2-KD cells migrated at significantly higher rates compared with their SUSD2 NT counterpart cell lines. Quantitative reverse transcription-PCR and western immunoblot analysis indicated an inverse relationship between SUSD2 and well-characterized mesenchymal proteins, including Twist-1, Zeb-1, N-cadherin, STEAP1, AHNAK, Snail-1, COL5A2 and Snail-3 in OVCAR3, OVSAHO and KURAMOCHI cell line models. In addition, OVCAR3 and KURAMOCHI SUSD2-KD spheroids displayed increased mesothelial clearance ability compared with cells that express endogenous levels of SUSD2. These data suggest that SUSD2 has a role in the inhibition of mesothelial clearance, which is required for metastasis. Altogether, our findings indicate that SUSD2 impedes migration, epithelial-to-mesenchymal transitional and mesothelial clearance of HGSOC cells, consistent with prolonged survival of patients with SUSD2-expressing tumors.

Dataset Information

PRMT8 demonstrates variant-specific expression in cancer cells and correlates with patient survival in breast, ovarian and gastric cancer.

Publications

PRMT8 demonstrates variant-specific expression in cancer cells and correlates with patient survival in breast, ovarian and gastric cancer.

Similar Datasets

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