Abstract
The import of proteins into the nucleus plays an important role in tumor development. In addition to the classical nuclear import proteins importin‐β and importin‐α, there are many nonclassical nuclear import proteins that include TNPO2. The role of TNPO2 as a nonclassical nuclear import protein in tumors is limited. Our previous studies have shown that DYNC1I1 is a poor prognostic factor for gastric cancer and can promote the proliferation and metastasis of gastric cancer cells. An expression profile chip showed that TNPO2 was its potential downstream. DYNC1I1 upregulated TNPO2 expression by upregulating SP1, following which, SP1 recruited and bound to the P300‐acetylated TNPO2 promoter region histones, and thus promoted TNPO2 expression. At the same time, TNPO2 promoted gastric cancer cell proliferation and inhibited apoptosis by a mechanism that might be depending on the functional expression of P21.
Highlights
Gastric carcinoma is one of the most common malignancies, with a relatively high rate of mortality across the world.[1]
The results showed that the Transportin 2 (TNPO2) transcription factor SP1 plays an important role, as it serves as a transcription factor and simultaneously recruits the P300‐acetylated TNPO2 promoter region histone
The luciferase activity in pGL4.10‐TNPO2 promoter (Mu) and pcDNA4.1‐SP1 cotransfection groups was not significantly higher when compared to normal control cells (Figure 2G).These observations demonstrated that DYNC1I1 decreased TNPO2 expression by downregulating SP1 expression in gastric cancer cells, further confirming that SP1 serves as a transcription factor of TNPO2
Summary
National Science and Technology Major Project of the Ministry of Science and Technology of China, Grant/Award Number: 2017ZX09304025; National Natural Science Foundation of China, Grant/Award Number: 81572374 and 31770963; Science and Technology Plan Project of Liaoning Province, Grant/ Award Number: 2016007010; The General Projects of Liaoning Province Colleges and Universities, Grant/Award Number: LFWK201706; Discipline Promotion Program of China Medical University, Grant/Award Number: 3110117058 and 111‐3110118026; The Key Research and Development Program of Liaoning Province, Grant/Award Number: 2018225060
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