miR-29a suppresses growth and metastasis in papillary thyroid carcinoma by targeting AKT3.
MicroRNA-29a (miR-29a) has been reported to play important roles in tumor initiation, development, and metastasis in various cancers. However, the biological function and potential mechanisms of miR-29a in papillary thyroid carcinoma (PTC) remain unclear. In the present study, we discovered that miR-29a was frequently downregulated in PTC tissues, and its expression was significantly associated with tumor size, TNM stage, and lymph node metastasis. Functional assays showed that overexpression of miR-29a markedly suppressed PTC cell proliferation, migration, and invasion and promoted PTC apoptosis and cell cycle arrest at G0/G1 phase. In vivo, miR-29a overexpression decreased tumor growth in a xenograft mouse model. Luciferase reporter assay showed that miR-29a can directly bind to the 3' untranslated region (UTR) of AKT3 in PTC cells. Overexpreesion of miR‑29a obviously decreased AKT3 expression, thereby suppressing phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation. We also confirmed that AKT3 expression was increased in PTC tissue and was inversely correlated miR-29a expression in PTC tissues. In addition, downregulation of AKT3 by siRNA mimicked the effects of miR-29a overexpression, and upregulation of AKT3 partially reversed the inhibitory effects of miR-29a. These results suggested that miR-29a could act as a tumor suppressor in PTC by targeting AKT3 and that miR-29a may potentially serve as an anti-tumor agent in the treatment of PTC.
Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, 130021, China.
Rui
R
Li
Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, 130021, China.
Jia
J
Liu
Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, 130021, China.
Qun
Q
Li
Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, 130021, China. chenguang518@aliyun.com.
Guang
G
Chen
Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, 130021, China. yuxiaofang1542@sina.cn.
Xiaofang
X
Yu
D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D002291:Carcinoma, Papillary / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D004794:Enzyme Repression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009368:Neoplasm Transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D047368:Tumor Burden
D020413:3' Untranslated Regions; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt
AKT3; Papillary thyroid carcinoma; Proliferation; miR-29a