ZNF148 modulates TOP2A expression and cell proliferation via ceRNA regulatory mechanism in colorectal cancer

Abstract

Background:Competing endogenous RNA (ceRNA) regulation is a novel hypothesized mechanism that states RNA molecules share common target microRNAs (miRNAs) and may competitively combine into the same miRNA pool.Methods:Zinc finger protein 148 (ZNF148) and TOP2A expression were analyzed in 742 colorectal cancer (CRC) tissues using immunohistochemistry (IHC). ZNF148 mRNA, TOP2A mRNA, miR101, miR144, miR335, and miR365 expression were estimated in 53 fresh frozen CRC tissues by reverse transcription polymerase chain reaction. Mechanisms underpinning ceRNA were examined using bioinformatics, correlation analysis, RNA interference, gene over-expression, and luciferase assays.Results:Protein levels of ZNF148 and TOP2A detected by IHC positively correlated (Spearman correlation coefficient [rs] = 0.431, P < 0.001); mRNA levels of ZNF148 and TOP2A also positively correlated (r = 0.591, P < 0.001). Bioinformatics analysis demonstrated that ZNF148 and TOP2A mRNA had 13 common target miRNAs, including miR101, miR144, miR335, and miR365. Correlation analysis demonstrated that levels of ZNF148 mRNA were negatively associated with levels of miR144, miR335, and miR365. Knockdown and overexpression tests showed that ZNF148 mRNA and TOP2A mRNA regulated each other in HCT116 cells, respectively, but not in Dicer-deficient HCT116 cells. Luciferase assays demonstrated that ZNF148 and TOP2A regulated each other through 3′UTR. Overexpression of ZNF148 mRNA and TOP2A mRNA caused significant downregulation of miR101, miR144, miR335, and miR365 in the HCT116 cells. We also found that knockdown of ZNF148 and TOP2A significantly promoted cell growth, and overexpression of ZNF148 and TOP2A inhibited cell proliferation, which was abrogated in Dicer-deficient HCT116 cells.Conclusion:ZNF148 and TOP2A regulate each other through ceRNA regulatory mechanism in CRC, which has biological effects on cell proliferation.

Identifying a Novel Biomarker TOP2A of Clear Cell Renal Cell Carcinoma (ccRCC) Associated with Smoking by Co-Expression Network Analysis

“…Our group had revealed TOP2A played a critical role in ccRCC carcinogenesis and progression, involving in the biological process of ccRCC proliferation 22 , 23 . Meanwhile, two publications suggested that TOP2A is overexpressed in colorectal cancer and hepatocellular carcinoma 24 , 25 , and overexpression of TOP2A was presumed to inhibit cell proliferation in colorectal cancer 26 . What's more, several investigators have reported that TOP2A is an independent prognostic biomarker in various cancer, such as nasopharyngeal carcinoma, breast cancer, pancreatic cancer and renal cell carcinoma 27 - 30 .…”

Long Noncoding RNA (lncRNA)-Mediated Competing Endogenous RNA Networks Provide Novel Potential Biomarkers and Therapeutic Targets for Colorectal Cancer

“…LncRNA DANCR exerts its oncogenic function on CRC tumor growth and liver metastasis through the DANCR/miR-577/HSP27 axis [41]. LncRNA ZNF148 induces cell proliferation in CRC via the ZNF148/miR-101,144,336,356/TOP2A axis [42]. LncRNA NEAT1 is proven to be positively associated with CRC tumor differentiation, metastasis, and TNM stages through the NEAT1/miR-495-3p/CDK6 axis [27,43].…”

LINC00922 Accelerates the Proliferation, Migration and Invasion of Lung Cancer Via the miRNA-204/CXCR4 Axis

“…The ceRNA hypothesis illustrated a novel regulatory network and provided a creative direction in investigating cellular function and molecular mechanism. Previous studies have already reported that several lncRNAs could bind to target miRNAs, thus regulating cellular behaviors of tumor cells [21][22][23][24]. For example, MALATI upregulates SLUG by absorbing miRNA-204, thus accelerating the progression of lung adenocarcinoma [25].…”