SCAMP3 is regulated by miR-128-3p and promotes the metastasis of hepatocellular carcinoma cells through EGFR-MAPK p38 signaling pathway.

PURPOSE

To explore the regulatory mechanism of secretory carrier membrane protein 3 (SCAMP3) and miR-128-3p in hepatocellular carcinoma (HCC).

PATIENTS AND METHODS

Cancer tissues and adjacent tissues of 52 HCC patients treated in our hospital were collected to explore the prognostic factors affecting their 3-year survival. HCC cells were purchased, the gene expression of Huh-7 and MHCC97 were adjusted by transfection, and the levels of SCAMP3, miR-128-3p, EGFR, p-EGFR, MAPK p38, p-MAPK p38, N-cadherin, vimentin, E-cadherin, cell proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT) were detected. A nude mouse model of HCC was constructed to verify the effects of transfection of mimics.

RESULTS

SCAMP3 was elevated in HCC patients and cancer tissues of HCC patients, while miR-128-3p showed opposite effects. High level SCAMP3 and low level miR-128-3p were related to poor prognosis of HCC. Both of them were correlated with excessive drinking history, N-stage, M-stage and pathological differentiation degree of HCC patients, as well as prognostic factors of HCC patients. SCAMP3 up-regulation or miR-128-3p down-regulation could promote HCC cell proliferation, migration, invasion, and transcription and protein levels of EGFR, p-EGFR, MAPK p38, p-MAPK p38, N-cadherin and vimentin, and inhibit HCC cell apoptosis and transcription and protein levels of E-cadherin. Dual luciferase reporter identified the targeting relationship between SCAMP3 and miR-128-3p. When both SCAMP3 and miR-128-3p were elevated or reduced, the biological manifestation of cells was not different from that of miR-NC transfected with unrelated sequences. Besides, miR-128-3p inhibited tumor growth in the HCC model in nude mice.

CONCLUSION

SCAMP3 can be controlled by miR-128-3p and can mediate the EGFR-MAPK p38 signaling pathway to inhibit HCC cell metastasis, which is expected to become a promising therapeutic target for HCC.