Dataset Information

Lon Peptidase 2, Peroxisomal (LONP2) Contributes to Cervical Carcinogenesis via Oxidative Stress.

ABSTRACT: BACKGROUND Lon protease is responsible for degrading proteins injured by oxidation, and has 2 isoforms, located in mitochondria and peroxisomes. Recent research showed that Lon protease was upregulated in different types of human cancer, but the role of Lon peptidase 2, peroxisomal (LONP2) in cancer is not well understood. It is known, however, that in cancer biology, reduction-oxidation is one of the molecular mechanisms involved in tumorigenesis. MATERIAL AND METHODS Oncomine databases and tissue microarrays, initially using immunohistochemistry, were used to analyze LONP2 expression in cervical cancer. In order to uncover the biologic functions and mechanism(s) underlying LONP2 in cervical tumorigenesis, we downregulated the expression of LONP2 using 2 siRNAs transduced in HeLa and SiHa cells. CCK8 assays were performed to evaluate cell viability. Cell cycle and apoptosis assays were used to determine cell growth. Cell migration and invasion assays were used to study changes in cell migration and invasion capacity. Immunofluorescence and flow cytometry were performed to analyze the changes in ROS production. RESULTS We found that the expression of LONP2 was significantly upregulated in cervical cancer, and there was a significant association with pathology type, pathology grade, and clinical stage, but not with age or lymph node metastasis. Moreover, we demonstrated that knocking down LONP2 in HeLa and SiHa cells reduced cell proliferation, cell cycle, apoptosis, migration, invasion, and oxidative stress levels. CONCLUSIONS Our findings suggest that LONP2 promotes cervical tumorigenesis via oxidative stress and may be a potential biomarker and therapeutic target in cervical cancer.

SUBMITTER: Wu W

PROVIDER: S-EPMC5846714 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lon Peptidase 2, Peroxisomal (LONP2) Contributes to Cervical Carcinogenesis via Oxidative Stress.

Wu Wanrong W Liu Fulin F Wu Kejia K Chen Yurou Y Wu Hanshu H Dai Guo G Zhang Wei W

Medical science monitor : international medical journal of experimental and clinical research 20180304

BACKGROUND Lon protease is responsible for degrading proteins injured by oxidation, and has 2 isoforms, located in mitochondria and peroxisomes. Recent research showed that Lon protease was upregulated in different types of human cancer, but the role of Lon peptidase 2, peroxisomal (LONP2) in cancer is not well understood. It is known, however, that in cancer biology, reduction-oxidation is one of the molecular mechanisms involved in tumorigenesis. MATERIAL AND METHODS Oncomine databases and tis ...[more]

PMID: 29502128

Similar Datasets

Project description:Little is known about the alterations in microRNA (miRNA) expression patterns during the consecutive stages of cervical cancer development and their association with chromosomal instability and epigenetic changes. We integrated miRNA expression profiles in normal cervical squamous epithelium, high-grade precancerous lesions (CIN2-3), squamous cell carcinomas (SCC) and adenocarcinomas (AdCAs) with previously generated chromosomal profiles of the same samples. In addition, the DNA methylation status of downregulated miRNAs located in a CpG island was determined. Significantly differential expression during the consecutive stages of cervical SCC development was observed for 106 miRNAs. Altered expression of 5 significantly differentially expressed miRNAs, hsa-miR-9 (1q23.2), hsa-miR-15b (3q25.32), hsa-miR-28-5p (3q27.3), hsa-miR-100 and hsa-miR-125b (both 11q24.1) was directly linked to frequent chromosomal alterations. Another 9 significantly downregulated miRNAs were located within a CpG island. Three of these 9 miRNAs, hsa-miR-203, hsa-miR-572, and hsa-miR-638, showed increased methylation in cervical cancer cell lines and HPV-immortalised cells compared to primary keratinocytes. Functional analyses were performed for hsa-miR-9, representing a potential oncogene with increased expression linked to a chromosomal gain, and hsa-miR-203, representing a potential tumour suppressor gene silenced by DNA methylation. Hsa-miR-9 and hsa-miR-203 were found to alter cell viability and anchorage independent growth in vitro, respectively, supporting their oncogenic and tumour suppressive function in cervical cancer. In conclusion, differential expression of 106 miRNAs, partly associated with chromosomal alterations and epigenetic changes, was observed during cervical SCC development. Altered expression of hsa-miR-9 and hsa-miR-203 was shown to be functionally relevant, underlining the importance of deregulated miRNA expression in cervical carcinogenesis. 10 squamous cell carcinomas of the cervix, 9 adenocarcinomas of the cervix, 18 high-grade cervical intraepithelial neoplasias (CIN2-3), and 10 cervical squamous epithelial samples with normal histology were analysed using single channel (Cy3) miRNA microarrays from Agilent (G4471A-016436).

Dataset Information

Lon Peptidase 2, Peroxisomal (LONP2) Contributes to Cervical Carcinogenesis via Oxidative Stress.

Publications

Lon Peptidase 2, Peroxisomal (LONP2) Contributes to Cervical Carcinogenesis via Oxidative Stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure