The expression of MYC is strongly dependent on the circular PVT1 expression in pure Gleason pattern 4 of prostatic cance
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ORIGINAL PAPER
The expression of MYC is strongly dependent on the circular PVT1 expression in pure Gleason pattern 4 of prostatic cancer Miyaka Umemori1,2 · Morito Kurata1 · Akiko Yamamoto1 · Kouhei Yamamoto1 · Sachiko Ishibashi1 · Masumi Ikeda1 · Kojiro Tashiro3 · Takahiro Kimura3 · Shun Sato2 · Hiroyuki Takahashi2 · Masanobu Kitagawa1 Received: 20 November 2019 / Accepted: 3 January 2020 © The Japanese Society for Clinical Molecular Morphology 2020
Abstract PVT1 is a long-noncoding RNA and is highly expressed in various cancers including prostate cancers with stabilizing MYC protein. To characterize the objective biological features of the different morphological components such as Gleason patterns (GP) in prostate cancer, biopsy specimens containing only single pure GP (GP3, GP4, GP5) are used to analyze the relationship between PVT1 expression and MYC protein expression. The expressions of PVT1 and MYC were analyzed by quantitative PCR and the labeling index (LI) of MYC protein by immunohistochemical staining. PVT1, MYC, and MYC protein were highly expressed in GP 4, and interestingly the expression between PVT1 and MYC LI significantly correlated only in GP 4. In vitro experiments, the expression of MYC protein was slightly reduced by small interfering RNA against PVT1, while strongly reduced against specifically circular PVT1, splicing variants derived from the PVT1. Taken together, the expression characteristics of PVT1, MYC, and MYC protein differed depending on the GP. In particular, circular PVT1 might be strongly involved in the stabilization of MYC protein in GP4 and suggest different biological features. Keywords MYC · PVT1 · Prostate cancer · Gleason pattern
Introduction Prostate cancer is the most common male genital malignancy in the world and the third leading cause of cancerrelated deaths in males [1]. Prostate-specific antigen (PSA) screening and a needle core biopsy are widely performed when prostate cancer is suspected. Treatments, such as radical prostatectomy, hormonal, or radiation therapy are available, but unfortunately 30–40% of cases will relapse Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00795-020-00243-9) contains supplementary material, which is available to authorized users. * Morito Kurata [email protected] 1
Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1‑5‑45 Yushima, Bunkyo‑ku, Tokyo 113‑8510, Japan
2
Department of Pathology, The Jikei University Hospital, Tokyo, Japan
3
Department of Urology, The Jikei University Hospital, Tokyo, Japan
[2]. The Gleason grading system, designed by Dr. Donald Gleason in 1966, classifies the aggressiveness of prostate cancer in five groups based on the morphological pattern of the tumors; the score is determined by the main pattern and the sub-pattern [3, 4]. This system plays an important role in determining a treatment plan for prostate cancer because it can help predict the risk of recurren
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