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Published on: July 17, 2020
SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal carcinoma
Yang Li1, Yumin Lv1, Chao Cheng2
1Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 510095, Guangdong, China.
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.
Insights
SPEN (SMART/HDAC1-associated repressor protein) promotes nasopharyngeal carcinoma (NPC) metastasis by activating PI3K/AKT and c-JUN signaling pathways. This axis targets HIPK2, increasing NPC cell migration and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- SPEN (SMART/HDAC1-associated repressor protein) is implicated in various cancers but its role in nasopharyngeal carcinoma (NPC) is unclear.
- Understanding SPEN's molecular mechanisms in NPC is crucial for developing targeted therapies.
Purpose of the Study:
- To elucidate the role and molecular mechanisms of SPEN in nasopharyngeal carcinoma (NPC) pathogenesis and metastasis.
- To investigate the signaling pathways and molecular interactions involving SPEN in NPC.
Main Methods:
- Analysis of SPEN mRNA and protein expression in NPC tissues and cells.
- Experimental manipulation of SPEN expression (knockdown) to assess its impact on NPC behavior.
- Investigation of downstream signaling pathways including PI3K/AKT, c-JUN, and microRNA interactions (miR-4652-3p).
- Assessment of SPEN's effect on the tumor suppressor HIPK2 and epithelial-mesenchymal transition (EMT).
Main Results:
- SPEN expression is upregulated in NPC tissues and cells, correlating with poor prognosis.
- SPEN knockdown suppresses NPC cell migration and invasion by inactivating PI3K/AKT and c-JUN signaling.
- SPEN induces miR-4652-3p expression, which targets HIPK2, a suppressor of EMT.
- SPEN activates PI3K/AKT/c-JUN signaling to promote miR-4652-3p expression, targeting HIPK2 and driving NPC metastasis.
Conclusions:
- SPEN acts as a promoter of NPC metastasis through a novel molecular mechanism.
- The SPEN/PI3K/AKT/c-JUN/miR-4652-3p/HIPK2 axis represents a potential therapeutic target for NPC treatment.
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