miR-144-3p Contributes to the Development of Thyroid Tumors Through the PTEN/PI3K/AKT Pathway

被引:23
作者
Cao, Hui-Ling [1 ]
Gu, Ming-Qiang [2 ]
Sun, Zhuo [3 ]
Chen, Zhong-Jian [2 ]
机构
[1] Shandong First Med Univ, Dept Head & Neck Surg, Chengwu Hosp, Heze 274200, Shandong, Peoples R China
[2] Shandong First Med Univ, Dept Gen Surg, Chengwu Hosp, Heze 274200, Shandong, Peoples R China
[3] Shandong First Med Univ, Dept Oncol, Chengwu Hosp, Heze 274200, Shandong, Peoples R China
关键词
miR-144-3p; PTEN/PI3K/AKT; EMT; thyroid cancer; biological mechanism; CELL-PROLIFERATION; APOPTOSIS; CANCER; PI3K/AKT; PTEN;
D O I
10.2147/CMAR.S265196
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To explore the expression and related mechanism of miR-144-3p and PTEN in thyroid cancer (TC). Patients and Methods: From February 2018 to November 2019, 62 patients with TC who received treatment in Chengwu Hospital Affiliated to Shandong First Medical University were collected. TC cells and human normal thyroid HTori-3 cells were purchased. The miR144-3p-inhibitor, miR-144-3p-mimics, empty vector plasmid (miRNA-NC), si-PTEN and shPTEN were transfected into B-CPAP and HTh-7 cells. The expressions of miR-144-3p and PTEN in the specimens were tested by qRT-PCR (qP). WB was used to detect the expression of Bcl-2, APR3, N-cadherin, Slug and Bax proteins in the cells. The cell proliferation was detected by MTT, and the cell invasion was tested by Transwell. The apoptosis was detected by flow cytometry (FC). Results: miR-144-3p was highly expressed and PTEN was weakly expressed in the patients' tissues. The AUC of miR-144-3p and PTEN was >0.8. miR-144-3p and PTEN were related to TNM stage, lymph node metastasis and differentiation degree of TC patients. The B-CPAP and HTh-7 with the greatest expression differences were selected for transfection. The expression of miR-144-3p in miR-144-3p-inhibitor group was significantly lower than that in NC group (P<0.01), and that in miR-144-3p-mimics group was significantly higher than that in NC group (p < 0.01). The expression of PTEN in si-PTEN group was significantly lower than that in NC group (P<0.01), while that in sh-PTEN group was significantly higher than that in NC group (P<0.01). Silencing miR-144-3p and overexpressing PTEN could inhibit cell proliferation, invasion and promote apoptosis. WB detection uncovered that silencing the miR-144-3p expression and overexpressing PTEN could inhibit the PI3K, Akt, p-AKT, Bcl-2, APR3 and cyclinD1 proteins and promote the up-regulation of Bax expression. Rescue experiments revealed that the cell proliferation, invasion and apoptosis were not different from NC after co-transfection of miR-144-3p-mimics+sh-PTEN and miR144-3p-inhibitor+si-PTEN into B-CPAP and HTh-7. Conclusion: Inhibition of miR-144-3p expression can up-regulate PTEN and affect cell proliferation, invasion and apoptosis, which may be a potential therapeutic target for TC.
引用
收藏
页码:9845 / 9854
页数:10
相关论文
共 30 条
[11]   Long non-coding RNA CASC2 improved acute lung injury by regulating miR-144-3p/AQP1 axis to reduce lung epithelial cell apoptosis [J].
Li, Hongbin ;
Shi, Huijuan ;
Gao, Min ;
Ma, Ning ;
Sun, Rongqing .
CELL AND BIOSCIENCE, 2018, 8
[12]   The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer [J].
Liang, Wei-Cheng ;
Fu, Wei-Ming ;
Wong, Cheuk-Wa ;
Wang, Yan ;
Wang, Wei-Mao ;
Hu, Guo-Xin ;
Zhang, Li ;
Xiao, Li-Jia ;
Wan, David Chi-Cheong ;
Zhang, Jin-Fang ;
Waye, Mary Miu-Yee .
ONCOTARGET, 2015, 6 (26) :22513-22525
[13]  
Lippi F., 2018, EC END MET RES, V3, P222
[14]   MiR-144-3p promotes the tumor growth and metastasis of papillary thyroid carcinoma by targeting paired box gene 8 [J].
Liu, Chang ;
Su, Chang ;
Chen, Yanchun ;
Li, Guang .
CANCER CELL INTERNATIONAL, 2018, 18
[15]   Thyroid cancer "epidemic" also occurs in low- and middle-income countries [J].
Lortet-Tieulent, Joannie ;
Franceschi, Silvia ;
Dal Maso, Luigino ;
Vaccarella, Salvatore .
INTERNATIONAL JOURNAL OF CANCER, 2019, 144 (09) :2082-2087
[16]   MicroRNA-Mediated Rescue of Fear Extinction Memory by miR-144-3p in Extinction-Impaired Mice [J].
Murphy, Conor P. ;
Li, Xiang ;
Maurer, Verena ;
Oberhauser, Michael ;
Gstir, Ronald ;
Wearick-Silva, Luis Eduardo ;
Viola, Thiago Wendt ;
Schafferer, Simon ;
Grassi-Oliveira, Rodrigo ;
Whittle, Nigel ;
Huttenhofer, Alexander ;
Bredy, Timothy W. ;
Singewald, Nicolas .
BIOLOGICAL PSYCHIATRY, 2017, 81 (12) :979-989
[17]   MicroRNA-196a promotes cell proliferation and inhibits apoptosis in human ovarian cancer by directly targeting DDX3 and regulating the PTEN/PI3K/AKT signaling pathway [J].
Ni, Jie ;
Chen, Li ;
Ling, Li ;
Wu, Mengfei ;
Ren, Qiongzhen ;
Zhu, Weipei .
MOLECULAR MEDICINE REPORTS, 2020, 22 (02) :1277-1284
[18]   Overexpression of Circular RNA ciRS-7 Abrogates the Tumor Suppressive Effect of miR-7 on Gastric Cancer via PTEN/PI3K/AKT Signaling Pathway [J].
Pan, Haiyan ;
Li, Tao ;
Jiang, Yugang ;
Pan, Congcong ;
Ding, Yuanlin ;
Huang, Zhigang ;
Yu, Haibing ;
Kong, Danli .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2018, 119 (01) :440-446
[19]   PTEN and PI3K/AKT in non-small-cell lung cancer [J].
Perez-Ramirez, Cristina ;
Canadas-Garre, Marisa ;
Angel Molina, Miguel ;
Jose Faus-Dader, Maria ;
Angel Calleja-Hernandez, Miguel .
PHARMACOGENOMICS, 2015, 16 (16) :1843-1862
[20]   miRNA-Directed Regulation of the Main Signaling Pathways in Thyroid Cancer [J].
Ramirez-Moya, Julia ;
Santisteban, Pilar .
FRONTIERS IN ENDOCRINOLOGY, 2019, 10