ATIP1 and ATIP3a, two isoforms of MTUS1/ATIP, suppressed proliferation and induced apoptosis in oral malignant tumor cells

doi:10.19438/j.cjoms.2021.05.006

Abstract

Abstract: PURPOSE: To investigate the role of MTUS1/ATIP in suppression of proliferation and induce apoptosis of oral malignant tumor cells. METHODS: The expression level of MTUS1/ATIP in oral malignant tumor cells (UM1, SACC-83) was detected. Oral malignant tumor cells were transfected with ATIP1 and ATIP3a vector for 48 h. Proliferation analysis was performed with MTT assay. Flow cytometry and immunofluorescence technique were employed to measure cell cycle and apoptosis of oral malignant tumor cells. The expression level of proteins ATIP1, ATIP3a, Caspase3, ERK1/2, pERK1/2 in oral malignant tumor cells transfected with ATIP1 and ATIP3a was detected by Western blotting. The data was analyzed using SPSS 19.0 software package. RESULTS: ATIP1, ATIP3a and ATIP3b were the major isoforms produced by MTUS1 gene and significantly decreased in oral malignant tumor cells [TSCC cell line UM1, parotid adenoid cystic carcinoma (ACC) tissue and cell line SACC-83]. Restoration of MTUS1 (ATIP1 and/or ATIP3a) expression induced anti-proliferative activities against oral malignant tumor cells (UM1 and SACC-83), with a cooperative effect between ATIP1 and ATIP3a. In TSCC cells, the inhibition rate of ATIP1 was approximately 38.8% (24 h) and 57.3% (48 h), the inhibition rate of ATIP3a was approximately 48.1% (24 h) and 56.5% (48 h); however, the inhibition rate increased to 93.5% (24 h) and 88.8% (48 h) with combined action of ATIP1 and ATIP3a in TSCC cell lines (P<0.05). A similar effect was observed in adenoid cystic carcinoma (ACC) cells (P<0.05). Over-expression of ATIP1 led to G1/G0 cell cycle arrest, whereas ATIP3a caused G2/M arrest (P<0.05). Both ATIP1 and ATIP3a induced apoptosis and inhibited phosphorylation of ERK1/2 (extracellular-regulated kinase). CONCLUSIONS: The results suggest that MTUS1 is a promising anticancer agent for oral malignant tumor and has apoptosis-inducing activities via ERK1/2 pathway.

Key words: Oral malignant tumor, MTUS1/ATIP, Proliferation, Apoptosis, ERK

CLC Number:

R739.8

ZHAO Ting-ting, FENG Yan-qing, HE Qian-ting, MO Yun-long, DONG En-en, WANG An-xun. ATIP1 and ATIP3a, two isoforms of MTUS1/ATIP, suppressed proliferation and induced apoptosis in oral malignant tumor cells[J]. China Journal of Oral and Maxillofacial Surgery, 2021, 19(5): 417-423.

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