MCM6 Promotes Hepatocellular Carcinoma Progression via the Notch Pathway: Clinical, Functional, and Genomic Insights

Abstract

Objective. To evaluate the expression profile of MCM6 in HCC and the relationship between MCM6 level and clinicopathological parameters through bioinformatics analysis of several databases. Methods. MCM expression level, clinical parameters, survival data, and gene set enrichment analysis were analyzed by bioinformatics database, including Oncomine™, UALCAN, HCCDB, TCGA, cBioPortal, and LinkedOmics. Real-time PCR, western blotting, and IHC staining were conducted to identify the expression of MCM6 in HCC compared to normal liver tissues. Results. Bioinformatics analysis indicated that the mRNA of MCM6 was obviously increased in multiple cancer types, especially in HCC. MCM6 level was positively associated with multiple clinical parameters (stage 3 and grades 3 and 4) and negatively associated with patient outcomes (overall survival). Moreover, enrichment of functions and signaling pathways analysis of MCM6 suggested that MCM6 might mediate DNA replication and cellular metabolism to promote the development and progression of HCC. Furthermore, IHC staining and western blotting indicated that the MCM6 was enhanced in HCC tissue, and MCM6 could promote HCC proliferation in activating Notch pathway via WB and bioinformatic analysis. Conclusion. This study actually revealed the expression and related functions of MCM6 in HCC. Furthermore, MCM6 is a carcinogenic role in activating Notch pathway to promote HCC cell proliferation, which may be a new prognostic biomarker and therapeutic target for HCC patients.

DNA replication: Mechanisms and therapeutic interventions for diseases

“…On the contrary, WGCNA combining with TCGA and GEO analysis identified that exceptional expression of MCM6 reflects pathologic stage of multiple tumors, serving as putative biomarkers for breast cancer, 285–287 gastric cancer, 288,289 renal cell carcinoma, 215,290,291 HCC, 292–295 and non‐small cell lung carcinoma 217,296,297 . Meanwhile, MCM7 is widely regarded as an extensive biomarker in multiple tumor types since its overexpression pattern 233,234,298–310 .…”

“…115,225,[273][274][275] Consistent with this notion, overexpression of MCM5 also associates with tumor stages, which appears to be potential diagnostic and prognostic markers in thyroid cancer, 276,277 ovarian cancer, 269,[278][279][280] bladder cancer, [281][282][283] and renal cell carcinoma. 284 On the contrary, WGCNA combining with TCGA and GEO analysis identified that exceptional expression of MCM6 reflects pathologic stage of multiple tumors, serving as putative biomarkers for breast cancer, [285][286][287] gastric cancer, 288,289 renal cell carcinoma, 215,290,291 HCC, [292][293][294][295] and non-small cell lung carcinoma. 217,296,297 Meanwhile, MCM7 is widely regarded as an extensive biomarker in multiple tumor types since its overexpression pattern.…”

Retracted: MCM6 Promotes Hepatocellular Carcinoma Progression via the Notch Pathway: Clinical, Functional, and Genomic Insights

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”