Background: Aberrant expression of p53 and its downstream gene p21 is closely related to alterations in cell cycle and cell proliferation, and is common among cancer patients. However, the underlying molecular mechanism has not been fully unravelled. ZER6 is a zinc-finger protein with two isoforms possessing different amino termini (Ntermini) in their proteins, p52-ZER6 and p71-ZER6. The biological function of ZER6 isoforms, as well as their potential involvement in tumourigenesis and the regulation of p53 remain elusive. Methods: The effect of ZER6 isoforms on p53 and p21 was determined using specific knockdown and overexpression. p52-ZER6 expression in tumours was analysed using clinical specimens, while gene modulation was used to explore p52-ZER6 roles in regulating cell proliferation and tumourigenesis. The mechanism of p52-ZER6 regulation on the p53/p21 axis was studied using molecular biology and biochemical methods. Findings: p52-ZER6 was highly expressed in tumour tissues, and was closely related with tumour progression. Mechanistically, p52-ZER6 bound to p53 through a truncated KRAB (tKRAB) domain in its N-terminus and enhanced MDM2/p53 complex integrity, leading to increased p53 ubiquitination and degradation. p52-ZER6silencing induced G 0-G 1 phase arrest, and subsequently reduced cell proliferation and tumourigenesis. Intriguingly, this regulation on p53 was specific to p52-ZER6, whereas p71-ZER6 did not affect p53 stability, most likely due to the presence of a HUB-1 domain. Interpretation: We identified p52-ZER6 as a novel oncogene that enhances MDM2/p53 complex integrity, and might be a potential target for anti-cancer therapy.

No abstract

No abstract

Nasopharyngeal carcinoma (NPC) is a malignant tumor that grows in the nasopharynx with a predilection in the fossa Rosenmuller. Epithelial malignancies are often found in populations of China and Southeast Asia, including Indonesia. The NPC incidence in year 2008 as many as 84,400 cases and 51,600 of these cases resulted in death. A total of 120 new cases per year NPC found in hospitals Prof. dr. Margono Soekarjo (RSMS), Purwokerto. The NPC is difficult to be diagnose caused its primary tumor lies closed to the skull base as well as various structures of vital organs. Therefore, methods that can detect early NPC required for inspection.The etiology of NPC is multifactorial consisting of genetic factors, factors of infection Epstein-Barr Virus (EBV) and environmental factors.EBV has two phases in the cycle of infection that is the phase of lytic and latent phase. BRLF1 has an important function as mediator transition from latent e NPC. The research aimed to analysis mRNA BRLF1 expression as a biomarker of NPC diagnosis by RT-PCR and to determine the positivity of RT-PCR method to detect the expression of mRNA BRLF1. The research design was cross sectional study. Samples were FFPE tumor biopsy of NPC WHO III and the total samples were 22 individu from Department of Pathology Anatomy, Prof. Dr. Margono SoekarjoHospital, Purwokerto with informed consent. The positivity of mRNA BRLF1 from FFPE tumor biopsy of NPC WHO III was in 63.6%indicating a high expression.. Keywords: mRNA BRLF1, Epstein-Barr Virus, FFPE, Nasopharyngeal Carcinoma AbstrakKarsinoma Nasofaring (KNF) adalah tumor ganas yang tumbuh di nasofaring dengan predileksi pada fosa Rosenmuller. Keganasan epitel sering ditemukan pada populasi Cina dan Asia Tenggara, termasuk Indonesia. Kejadian KNF di tahun 2008 sebanyak 84.400 kasus dan 51.600 kasus ini mengakibatkan kematian. Sebanyak 120 kasus baru per tahun KNF ditemukan di RSUD dr. Dr. Margono Soekarjo (RSMS), Purwokerto. KNF sulit untuk didiagnosis karena tumor utamanya terletak dekat dengan dasar tengkorak serta berbagai struktur organ vital. Oleh karena itu, metode yang dapat mendeteksi KNF awal diperlukan untuk pemeriksaan. Etiologi KNF bersifat multifaktorial yang terdiri dari faktor genetik, faktor infeksi Virus Epstein-Barr (EBV) dan faktor lingkungan. EBV memiliki dua fase dalam siklus infeksi yaitu fase fase litik dan laten. BRLF1 memiliki fungsi penting sebagai mediator transisi dari laten ke fase litik. Ekspresi mRNA BRLF1 yang dilakukan dengan metode RT-PCR dapat digunakan untuk mendukung diagnosis KNF, sehingga metode ini dapat meningkatkan efisiensi pemeriksaan KNF. Penelitian ini bertujuan untuk menganalisis ekspresi mRNA BRLF1 sebagai biomarka diagnosis KNF dengan teknik RT-PCR dan untuk mengetahui sensitivitas metode RT-PCR untuk mendeteksi ekspresi mRNA BRLF1. Desain penelitiannya adalah penelitian cross sectional. Sampel adalah biopsi tumor FFPE dari pasien KNF WHO III dan total sampel adalah 22 individu pada Departmen Patologi Anatomi, Rumah Sakit Prof. Dr. Margono Soekarjo, Pu...