SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal carcinoma.

Abstract

SPEN family transcriptional repressor (SPEN), also known as the SMART/HDAC1-associated repressor protein (SHARP), has been reported to modulate the malignant phenotypes of breast cancer, colon cancer, and ovarian cancer. However, its role and the detail molecular basis in nasopharyngeal carcinoma (NPC) remain elusive. In this study, the SPEN mRNA and protein expression was found to be increased in NPC cells and tissues compared with nonmalignant nasopharyngeal epithelial cells and tissues. Elevated SPEN protein expression was found to promote the pathogenesis of NPC and lead to poor prognosis. Knockdown of SPEN expression resulted in inactivation ofPI3K/AKT and c-JUN signaling, thereby suppressing NPC migration and invasion. In addition, miR-4652-3p was found to be a downstream inducer of SPEN by targeting the homeodomain interacting protein kinase 2 (HIPK2) gene, a potential tumor suppressor that reduces the activation of epithelial-mesenchymal transition (EMT) signaling, thereby reducing its expression and leading to increased NPC migration, invasion, and metastasis. In addition, SPEN was found to induce miR-4652-3p expression by activating PI3K/AKT/c-JUN signaling to target HIPK2. Our data provided a new molecular mechanism for SPEN as a metastasis promoter through activation of PI3K/AKT signaling, thereby stimulating the c-JUN/miR-4652-3p axis to target HIPK2 in NPC.

• Authors: Yang Li, Yumin Lv, Chao Cheng, Yan Huang, Liu Yang, Jingjing He, Xingyu Tao, Yingying Hu, Yuting Ma, Yun Su, Liyang Wu, Guifang Yu, Qingping Jiang, Shu Liu, Xiong Liu, Zhen Liu
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 7 Pg. 509 (07 02 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 32641685 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• DNA-Binding Proteins
• MIRN4652 microRNA, human
• MicroRNAs
• Proto-Oncogene Proteins c-jun
• RNA-Binding Proteins
• SPEN protein, human
• HIPK2 protein, human
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Carrier Proteins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (genetics)
• DNA-Binding Proteins (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Nasopharyngeal Carcinoma (genetics, pathology)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Phosphatidylinositol 3-Kinases (metabolism)
• Prognosis
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-jun (metabolism)
• RNA-Binding Proteins (metabolism)
• Signal Transduction