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SZRD1 is a Novel Protein that Functions as a Potential Tumor Suppressor in Cervical Cancer.

ABSTRACT: SZRD1 is a novel gene screened out by high-throughput platform, and so far there exists no systematic function reports. The purpose of our study is to discover the function and mechanism of this novel human gene. Bioinformatics analysis indicates that SZRD1 is a highly conserved intracellular protein. After overexpression of SZRD1, we found that SZRD1 could arrest the cell cycle in G2 phase and play a role in inhibiting cell proliferation and inducing apoptosis. In contrast, after knockdown of endogenous SZRD1, we concluded that it could promote cell proliferation. The mechanism investigations showed that overexpression of SZRD1 could downregulate the phosphorylation of ERK1/2, AKT, STAT3 and downstream signaling molecules, and then arrest the cells in G2 phase by upregulating P21. Tissue microarray analysis showed that the expression of SZRD1 was downregulated in cervical squamous cell carcinomas compared with normal squamous epithelium, and the ratio of downregulation correlated with the stage of the cancer. Overall, we clarified the function of this novel protein SZRD1, which indicated it may be a potential novel tumor suppressor in cervical cancer.

SUBMITTER: Zhao N

PROVIDER: S-EPMC5559976 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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SZRD1 is a Novel Protein that Functions as a Potential Tumor Suppressor in Cervical Cancer.

Zhao Ning N Zhang Guoying G He Minwei M Huang He H Cao Lulu L Yin Ang A Wang Pingzhang P Wang Lu L

Journal of Cancer 20170714 11

<i>SZRD1</i> is a novel gene screened out by high-throughput platform, and so far there exists no systematic function reports. The purpose of our study is to discover the function and mechanism of this novel human gene. Bioinformatics analysis indicates that SZRD1 is a highly conserved intracellular protein. After overexpression of SZRD1, we found that SZRD1 could arrest the cell cycle in G2 phase and play a role in inhibiting cell proliferation and inducing apoptosis. In contrast, after knockdo ...[more]

PMID: 28819415

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Project description:Previous microRNA (miR) microarray analysis revealed that miR‑218 is downregulated in cervical cancer tissues. The present study aimed to further evaluate the expression of miR‑218 in cervical cancer specimens, determine the association between its expression with disease progression, and investigate the roles of miR‑218 in cervical cancer cells. Tissue specimens were obtained from 80 patients with cervical squamous cell carcinoma, 30 patients with high‑grade cervical intraepithelial neoplasia [(CIN) II/III] and 15 patients with low‑grade CIN (CINI); in addition, 60 plasma samples were obtained from patients with cervical cancer, and 15 normal cervical tissue specimens and 30 plasma samples were obtained from healthy women. These samples were used for analysis of miR‑218 expression via reverse transcription‑-quantitative PCR. In addition, tumor cells were transfected with miR‑218 mimics, human papillomavirus (HPV)16 E6/E7 small interfering RNA, or their respective negative controls to determine the viability, colony formation, migration and invasion of cells using MTT, colony formation, wound healing and Transwell assays, respectively. Target genes of miR‑218 were bioinformatically predicted and analyzed using Gene Ontology (GO) terms. The results revealed that miR‑218 was downregulated in the tumor tissues and plasma of patients with cervical cancer, with expression associated with the advanced clinicopathological characteristics of patients, including HPV positivity, tumor size, blood vessel invasion and lymph node metastasis. Furthermore, miR‑218 overexpression reduced tumor cell viability and xenograft growth, and suppressed tumor cell migration and invasion. HPV was detected in 75% of the 80 patients with cervical cancer, and HPV positivity was inversely associated with miR‑218 expression. In addition, bioinformatics analysis predicted that roundabout guidance receptor 1 (ROBO1) was a target gene of miR‑218; miR‑218 overexpression significantly reduced ROBO1 levels. Furthermore, GO analysis revealed that ROBO1 was involved in regulating cell proliferation, adhesion and migration, and the cell cycle. In conclusion, the findings of the present study suggested that miR‑218 may possess antitumor activities in cervical cancer.

Dataset Information

SZRD1 is a Novel Protein that Functions as a Potential Tumor Suppressor in Cervical Cancer.

Publications

SZRD1 is a Novel Protein that Functions as a Potential Tumor Suppressor in Cervical Cancer.

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