miR-506 acts as a tumor suppressor by directly targeting the hedgehog pathway transcription factor Gli3 in human cervical cancer

Abstract

Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.

Suppression of forkhead box Q1 by microRNA-506 represses the proliferation and epithelial-mesenchymal transition of cervical cancer cells

“…In the present study, we demonstrated the critical role of miR-506 in cervical cancer. Our results were consistent with those of a recent study that reported that miR-506 is significantly downregulated in cervical cancer tissues (42). These authors further demonstrated that miR-506 overexpression suppressed the growth and enhanced apoptosis and chemosensitivity of cervical cancer cells by targeting Gli3 (42).…”

“…Our results were consistent with those of a recent study that reported that miR-506 is significantly downregulated in cervical cancer tissues (42). These authors further demonstrated that miR-506 overexpression suppressed the growth and enhanced apoptosis and chemosensitivity of cervical cancer cells by targeting Gli3 (42). Overall, decreased miR-506 expression may result in the overexpression of oncogenes, such as FOXQ1, which contributes to the development and progression of cervical cancer.…”

MicroRNA-138 inhibits proliferation, migration and invasion through targeting hTERT in cervical cancer

“…Li et al (27) reported that the overexpression of miR-342-3p inhibits cell proliferation, migration and invasion in cervical cell lines by targeting mammalian transcription factor forkhead box M1. Wen et al (28) reported that miR-506 induced cell cycle arrest at the G1/S transition, enhanced the apoptosis and chemosensitivity of cervical cancer cells, and inhibited cervical cancer growth in vitro and in vivo. Data from the current study provides evidence that miR-138 can inhibit proliferation, colony formation, migration and invasion, induce cell apoptosis in cervical cancer cells, and suppress tumor growth in nude mice models.…”

miR-506 suppresses neuroblastoma metastasis by targeting ROCK1

“…In the present study, it was demonstrated that miR-506 functions as a tumor suppressor in neuroblastoma by directly targeting ROCK1. Previous studies have reported that the expression of miR-506 is reduced in numerous types of cancer, including epithelial ovarian cancer (15)(16)(17)(18), hepatocellular carcinoma (19), cervical cancer (20), lung cancer (21), breast cancer (22) and colon cancer (23), and is involved in cancer progression, notably cell proliferation, metastasis and apoptosis. In the current study, it was observed that miR-506 was decreased in neuroblastoma tissues and cell lines when compared to normal tissues, supporting the notion that miR-506 functions as a potential tumor suppressor.…”

“…Additionally, the results demonstrated that miR-506 inhibited neuroblastoma cell proliferation and metastasis. The previously reported target genes of miR-506 include cyclin-dependent kinase4/6-forkhead box protein M1 (18), yes-associated protein (19), GLI family zinc finger 3 (20), nuclear factor-κB p65 (21) and others. In the present study, it was verified that ROCK1 was a novel target gene for miR-506 in neuroblastoma.…”