MicroRNA-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of PTEN

Autor: Alissa Michelle Go Wong, Victor Ho Fun Lee, Kar Lok Kong, Li Yi Zhang, Sui Sui Dong, Ying Hui Zhu, Dora L.W. Kwong, Xin Yuan Guan, Sai Wah Tsao, Li Fu, Juan Chen
Rok vydání: 2012
Předmět:
Adult
Male
Cancer Research
Tumor suppressor gene
Blotting
Western
Mice
Nude
Apoptosis
Biology
medicine.disease_cause
Real-Time Polymerase Chain Reaction
Immunoenzyme Techniques
Mice
Phosphatidylinositol 3-Kinases
Cell Movement
Nasopharynx
medicine
Cell Adhesion
Tumor Cells
Cultured
Tensin
PTEN
Animals
Humans
Neoplasm Invasiveness
RNA
Messenger
PI3K/AKT/mTOR pathway
Aged
Cell Proliferation
Mice
Inbred BALB C
Nasopharyngeal Carcinoma
Akt/PKB signaling pathway
Reverse Transcriptase Polymerase Chain Reaction
Carcinoma
Cell Cycle
PTEN Phosphohydrolase
Nasopharyngeal Neoplasms
General Medicine
Cell cycle
Middle Aged
medicine.disease
Gene Expression Regulation
Neoplastic
MicroRNAs
Nasopharyngeal carcinoma
Case-Control Studies
Cancer research
biology.protein
Female
Carcinogenesis
Proto-Oncogene Proteins c-akt
Zdroj: Carcinogenesis. 34(2)
ISSN: 1460-2180
Popis: Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with significantly high prevalence in Southern China. Unlike other head and neck cancers, mutations or deletions of tumor suppressor genes in NPC are not common. Recently, downregulation of tumor suppressor genes expression by microRNA (miRNA) is increasingly recognized as an important mechanism of nasopharyngeal tumorigenesis. In this study, we reported that microRNA-144 (miR-144) was frequently upregulated in NPC specimens and cell lines. Repression of miR-144 significantly decreased cell proliferation, clonogenicity, migration, invasion and tumor formation in nude mice, while restoring miR-144 in miR-144-attenuated NPC cells exhibited a strong tumorigenic role. Further, we found that miR-144 was inversely correlated with the tumor suppressor gene phosphatase and tensin homolog (PTEN) in NPC specimens and cell lines, and then we identified PTEN as a direct target of miR-144 in NPC cell lines. PTEN downregulation in miR-144-attenuated cells could increase cell growth, migration and invasion. Mechanistic investigations revealed that miR-144 suppressed the expression of PTEN to increase the expression of pAkt and cyclin D1 to promote G(1)-phase transition and decrease E-cadherin to promote migration and invasion. Taken together, we provide compelling evidence that miR-144 functions as an onco-miRNA in NPC, and its oncoeffects are mediated chiefly by repressing PTEN expression to activate the PI3K/Akt pathway.
Databáze: OpenAIRE
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