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

Abstract

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.

Comparison of miRNA and gene expression profiles between metastatic and primary prostate cancer

“…miR-144 has been reported to improve the growth of HeLa cells (19), suggesting its role in tumor cell proliferation. Zhang et al (20) have proposed that miR-144 promotes the malignant progression of nasopharyngeal carcinoma cells by targeting the tumor-suppressor gene phosphatase and tensin homolog; however, its role in PC -33 has not been reported thus far, to the best of our knowledge. In the present study, numerous DEGs were observed to be downregulated by miR-144.…”

A Critical Role of miR-144 in Diffuse Large B-cell Lymphoma Proliferation and Invasion

“…Based upon the abundant data accumulated during the past two decades, scientists began to argue for use of miRNAs as novel therapeutic targets for various malignancies (33). MiR-144 has been implicated in both oncogenic and tumorsuppressive roles in different tumors, but its role in DLBCL is not yet clarified (34)(35)(36). Although research on the true biologic relevance of miR-144 in cancer is still in its infancy, in this study we focused on the expression and function of miR-144 in DLBCL.…”

Upregulation of microRNA-337 promotes the proliferation of endometrial carcinoma cells via targeting PTEN

“…miR-21 was one of the earliest miRs in which its inhibition was demonstrated to elevate PTEN levels and reduce tumor cell proliferation, invasion and migration in human hepatocellular cancer (34). Later studies suggested that PTEN may be a target of miR-22, miR-221/222 and miR-144 in different types of malignancy (35)(36)(37). In the present study, the binding of miR-337 to 3'-UTR of PTEN mRNA downregulated PTEN mRNA and protein expression levels.…”