<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

Abstract

Introduction: CD24 is known as a heavily glycosylated cell surface molecule that is highly expressed in a wide variety of human malignancies. Previous studies have shown that CD24 plays an important role in self-renewal, proliferation, migration, invasion and drug resistance of hepatocellular carcinoma (HCC). However, little is known about the expression and function of CD24 isoform a (CD24A) and CD24 isoform b (CD24B) in HCC. Materials and methods: Quantitative real-time polymerase chain reaction (qPCR) and Western blotting were performed to detect CD24 and EGR1 expression in HCC cells and tissue. The function of CD24 in cell proliferation was verified with MTT assays, colony formation assays and tumor xenograft models. Wound healing assays and invasion assays were performed to clarify the function of CD24 in the regulation of cell migration and invasion in HCC. A dual luciferase reporter assay and chromatin immunoprecipitation assay were used to analyze the regulation mechanism of CD24A. Results: CD24A but not CD24B, which was barely detected by qPCR and Western blotting, is significantly upregulated in HCC tissue. Both CD24A and CD24B contribute to HCC cell proliferation, migration and invasion, but CD24A is more effective than CD24B. EGR1 downregulates CD24A and exerts transcription-promoting activity on the CD24A promoter. Furthermore, EGR1 represses HCC cell proliferation via downregulation of CD24A. Conclusion: CD24A is the predominant CD24 isoform in HCC and plays a major role in cell proliferation, migration, and invasion. EGR1 can exert its antitumor effect through transcriptional downregulation of CD24A in HCC.

Identification of Gene Signatures for Diagnosis and Prognosis of Hepatocellular Carcinomas Patients at Early Stage

“…The protein encoded by EGR1 is a nuclear protein and functions as a transcriptional regulator. EGR1 was confirmed as a cancer suppressor by targeting CD24A in HCC (Li et al, 2019). Compared with the EGR1, SRY-box transcription factor 17 (SOX17) has been confirmed as the transcription factor with significant protein-altering mutations by WGCNA and GeNets.…”

Reduced DAXX Expression Is Associated with Reduced CD24 Expression in Colorectal Cancer

“…In addition, CD24 was overexpressed in aggressive HCC cell lines and the tumor tissues of patients with recurrent HCC based on the expression of EGR, an early growth response protein. CD24 expression was positively correlated with malignancy in HCC [62]. In the human lung carcinoma model A549, CD24 expression increased the expression of p-STAT3 (Y705), p-FAK (Y925), and p-Src (Y416) via Src, therefore it is associated with a poor prognosis of cancer [63].…”

Novel insights into the function of CD24: A driving force in cancer

“…Two transcripts, termed CD24A and CD24B, were identified. They differed in length and only shared approximately 47% amino acid identity 109 . The variant CD24A, but not CD24B, which was barely detected by qPCR and western blotting, was significantly upregulated in HCC tissue 109 .…”

“…A recent study involving HCC examined in more detail transcripts from the CD24 gene located on chromosome 6q21 109 . Two transcripts, termed CD24A and CD24B, were identified.…”

“…They differed in length and only shared approximately 47% amino acid identity 109 . The variant CD24A, but not CD24B, which was barely detected by qPCR and western blotting, was significantly upregulated in HCC tissue 109 . When overexpressed in recipient cells, both CD24A and CD24B contributed to cell proliferation, migration and invasion.…”