miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis

Abstract

Malignant glioma is an often fatal type of cancer. Aberrant activation of STAT3 leads to glioma tumorigenesis. STAT3- induced transcription of protein-coding genes has been extensively studied; however, little is known about STAT3-regulated miRNA gene transcription in glioma tumorigenesis. In this study, we found that abnormal activation or decreased expression of STAT3 promotes or inhibits the expression of miR-182- 5p, respectively. Bioinformatics analyses determined that tumor suppressor protocadherin-8 (PCDH8) is a candidate target gene of miR-182-5p. miR-182-5p negatively regulated PCDH8 expression by directly targeting its 3'-untranslated region. PCDH8 knockdown induced the proliferative and invasive capacities of glioma cells. Silencing of PCDH8 or miR-182-5p mimics could reverse the inhibitory effect of WP1066, a STAT3 inhibitor, or STAT3 knockdown in vitro and in vivo on glioma progression. Clinically, expression levels of PCDH8 were inversely correlated with those of p- STAT3 or miR-182-5p in glioblastoma tissues. These findings reveal that the STAT3/miR-182-5p/PCDH8 axis has a critical role in glioma tumorigenesis and that targeting the axis may provide a new therapeutic approach for human glioma.

Targeting of miR‐31/96/182 to the Numb gene during head and neck oncogenesis

“…The miR‐31 is upregulated by EGF treatment and AKT activation in HNSCC cells . The miR‐96 and miR‐182 are known to be upregulated by many oncogenic stimuli in other malignancies . This study further shows that ERK and p38 activation is also able to slightly upregulate miR‐96 and miR‐182 in HNSCC cells.…”

“…The miR‐96 and miR‐182 , members of the miR‐183/96/182 cluster, are oncogenic during a variety of malignancies . The epidermal growth factor receptor pathway has been reported to trans‐activate miR‐96 expression in prostate carcinoma .…”

“…High miR‐96 expression has been noted in cervical squamous cell carcinoma that is positive for human papillomavirus‐16 . Multiple oncogenic signals, including those of the androgen receptor pathway, stat3, and MyoD, are known to upregulate miR‐182 expression in neoplasms . Moreover, the ß‐catenin/TCF pathway has been found to trans‐activate the transcription of the miR‐183/96/182 cluster .…”

“…The miR-96 and miR-182, members of the miR-183/96/ 182 cluster, 22 are oncogenic during a variety of malignancies. 12,[23][24][25][26][27][28][29][30][31] The epidermal growth factor receptor pathway has been reported to trans-activate miR-96 expression in prostate carcinoma. 26 High miR-96 expression has been noted in cervical squamous cell carcinoma that is positive for human papillomavirus-16.…”

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1

“…Inhibiting miR-182-5p by regulating CASP9 expression confers pro-apoptotic and anti-proliferative effects in human breast cancer [23]. Activated STAT3 induces miR-182-5p expression, which has been found to enhance the growth of glioma tumors [24]. Our study is the first to outline a role for miR-182-5p in the proliferation of OSCC cells.…”