Eur Rev Med Pharmacol Sci 2021; 25 (3): 1330-1338
DOI: 10.26355/eurrev_202102_24839

HMGN5 promotes invasion and migration of colorectal cancer through activating FGF/FGFR pathway

G.-J. Zhu, F. Liu, Y.-G. Xu, C.-X. Zhao, J.-G. Zhao, C. Sun

Surgery Intensive Care Unit, Children’s Hospital of Soochow University, Suzhou, China. sunchao0819@suda.edu.com


OBJECTIVE: To detect the expression of high-mobility group nucleosome-binding domain 5 (HMGN5) in colorectal cancer tissues, to explore the function of HMGN5 on the proliferation and metastasis of colorectal cancer cells, and to further study the molecular mechanism of HMGN5 in the malignant progression of colorectal cancer (CRC).

PATIENTS AND METHODS: The cancer tissues and para-carcinoma tissues were harvested from 40 patients with CRC. The expression of HMGN5 was detected via quantitative real-time polymerase chain reaction (qRT-PCR), and the relation between HMGN5 and clinical indexes of CRC patients was further analyzed. The CRC HT29 and HCT116 cell lines with high expression levels of HMGN5 were selected, and the HMGN5 knockdown model was established. The functions of HMGN5 on CRC cells were stated by cell counting kit-8 (CCK-8) assay and transwell migration assay. Then, the association between HMGN5 and fibroblast growth factor 12 (FGF12) was further explored via Dual-Luciferase reporter assay and reverse assay.

RESULTS: The qRT-PCR showed that HMGN5 expression was significantly rising in cancer tissues compared to the control group. The incidence rate of lymph node metastasis and distant metastasis was higher in higher expression HMGN5 group than the lower expression HMGN5 group. The results of cell function experiments revealed that silence of HMGN5 could suppress the proliferation and migration of HT29 and HCT116. In addition, it was found using qRT-PCR that knockdown of HMGN5 could significantly down-regulate the expressions of FGF12, FGFR, PI3K and AKT in HT29 and HCT116 cells. The targeted binding relation between HMGN5 and FGF12 was also indicated by the dual-luciferase reporter assay. The consequence of qRT-PCR manifested that FGF12 expression markedly rose in CRC tissues, which had a positive correlation with HMGN5. Moreover, reverse assay indicated that the inhibitory effect of HMGN5 knockdown on the malignant progression of CRC could be reversed by recombinant FGF12, indicating once again that there is a mutual regulatory effect between HMGN5 and FGF12.

CONCLUSIONS: HMGN5 can increase the proliferative and migrative capacity of CRC cells via targeted binding to FGF12. In addition, clinical data analyses demonstrate that HMGN5 is intimately related to the incidence rate of lymph node metastasis and distant metastasis in patients with CRC.

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To cite this article

G.-J. Zhu, F. Liu, Y.-G. Xu, C.-X. Zhao, J.-G. Zhao, C. Sun
HMGN5 promotes invasion and migration of colorectal cancer through activating FGF/FGFR pathway

Eur Rev Med Pharmacol Sci
Year: 2021
Vol. 25 - N. 3
Pages: 1330-1338
DOI: 10.26355/eurrev_202102_24839