Dataset Information

LncRNA WT1-AS inhibits the aggressiveness of cervical cancer cell via regulating p53 expression via sponging miR-330-5p.

ABSTRACT:

Background

Emerging evidences have demonstrated that lncRNAs play vital roles in various pathological processes, including cancer. The lncRNA WT1 antisense RNA (WT1-AS) serves as a tumor suppressor in various cancers. Nevertheless, the expression and precise function of WT1-AS in cervical carcinoma still remain not yet investigated. The objective of our study was to explore the expression of WT1-AS and its biological roles in cervical cancer.

Methods

Differences in the lncRNA expression profiles between cervical cancer and adjacent normal tissues were assessed by lncRNA expression microarray analysis. The expression of p53 in cervical cancer cell was assessed by qRT-PCR and immunofluorescence assay. Loss-of-function studies were used to explore the effect of lncRNA WT1-AS on the growth and metastasis of cervical cancer cell in vitro and in vivo.

Results

Our results demonstrated that WT1-AS was remarkably down-regulated in cervical carcinoma. Functional assays proved that up-regulation of WT1-AS significantly suppressed cervical cancer cell proliferation, migration and invasion. In addition, the luciferase reporter assay identified that miR-330-5p was the target of WT1-AS. Moreover, tumor suppressor p53 was identified as the direct target of miR-330-5p and alternation of miR-330-5p/p53 axis reversed the effects of WT1-AS in cervical cancer cell.

Conclusion

Altogether, our findings suggested that WT1-AS was down-regulated in cervical carcinoma and WT1-AS suppressed cervical carcinoma cell- proliferation, migration and invasion through regulating the miR-330-5p/p53 axis.

SUBMITTER: Cui L

PROVIDER: S-EPMC6331070 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

lncRNA WT1-AS inhibits the aggressiveness of cervical cancer cell via regulating p53 expression via sponging miR-330-5p.

Cui LiJuan L Nai ManMan M Zhang Ke K Li Lu L Li RuiMin R

Cancer management and research 20190111

<h4>Background</h4>Emerging evidences have demonstrated that lncRNAs play vital roles in various pathological processes, including cancer. The lncRNA WT1 antisense RNA (WT1-AS) serves as a tumor suppressor in various cancers. Nevertheless, the expression and precise function of WT1-AS in cervical carcinoma still remain not yet investigated. The objective of our study was to explore the expression of WT1-AS and its biological roles in cervical cancer.<h4>Methods</h4>Differences in the lncRNA expr ...[more]

PMID: 30666161

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Project description:Circular RNAs (circRNAs) are a new class of single-stranded RNAs that form a continuous loop with crucial role in regulation of gene expression. Because their circular conformation conforms numerous properties, circRNAs have been investigated recently to demonstrate their important role in the development and progression of various cancers. However, the function of circRNAs and their regulatory outcomes in cervical cancer (CC) have rarely been explored. In this study, the role and molecular mechanism of hsa_circ_0107593 in cervical cancer are demonstrated. Quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of hsa_circ_0107593 and three miRNAs (hsa-miR-20a-5p, 93-5p, and 106b-5p) in paired CC tissues (tumor tissue vs. adjacent normal cervical tissue), CC cell lines, and human normal cervical epithelial immortalized cell line. A series of functional experiments were conducted to assess the function of hsa_circ_0107593 in CC development. The Receiver Operating Characteristic (ROC) curve was plotted to estimate the diagnostic value of hsa_circ_0107593 in CC. The dual-luciferase reporter assay was used to explore the interaction between hsa_circ_0107593 and hsa-miR-20a-5p/93-5p/106b-5p. Bioinformatic analysis was conducted to predict the target mRNAs, pathways, and functional enrichment. The results revealed that hsa_circ_0107593 has low expression in CC tissues and CC cell lines. Moreover, negative correlations of hsa_circ_0107593 expression were found against tumor diameter, FIGO stage, and myometrial invasion. Also, hsa_circ_0107593 impedes CC cell proliferation, migration, and invasion. Based on ROC curve analysis, hsa_circ_0107593 could serve as a diagnostic biomarker. Its low expression may indicate increased patient's risk to developing cervical cancer. Mechanistically, hsa_circ_0107593 serves as a sponge of hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p. Collectively, our study implies that hsa_circ_0107593 has tumor-suppressing activity in CC by physically binding with hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p.