LINC-PINT Suppresses the Aggressiveness of Thyroid Cancer by Downregulating miR-767-5p to Induce TET2 Expression

被引：33

作者：

Jia, Meng ^{[1
]}

Li, Zhuyao ^{[1
]}

Pan, Mengjiao ^{[1
]}

Tao, Mei ^{[1
]}

Wang, Jiaxiang ^{[2
]}

Lu, Xiubo ^{[1
]}

机构：

[1] Zhengzhou Univ, Dept Thyroid Surg, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China

[2] Zhengzhou Univ, Dept Pediat Surg, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2020年 / 22卷

关键词：

growth; invasion; LINC-PINT; miR-767-5p; thyroid cancer;

D O I：

10.1016/j.omtn.2020.05.033

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Long noncoding RNA (lncRNA) long intergenic nonprotein-coding RNA, p53-induced transcript (LINC-PINT) has shown anti-invasive activity in lung and colon cancer cells. However, the role of LINC-PINT in thyroid cancer is unclear. In the present work, we explored the expression of LINC-PINT in 60 paired thyroid cancer and adjacent normal tissues. The clinical significance and biological function of LINC-PINT in thyroid cancer were determined. LINC-PINT expression was downregulated in thyroid cancer relative to adjacent normal tissues (p = 0.0002). Low expression of LINC-PINT was significantly associated with advanced tumor node metastasis (TNM) stage (p = 0.0306) and lymph node metastasis (p = 0.0359). Ectopic expression of LINC-PINT suppressed the proliferation, invasion, and tumorigenesis of thyroid cancer cells. Mechanistically, LINC-PINT associated with and downregulated microRNA (miR)767-5p. Moreover, LINC-PINT overexpression relieved miR-767-5p-mediated repression of ten-eleven translocation 2 (TET2). miR-767-5p promoted aggressiveness of thyroid cancer, which was reversed by overexpression of TET2. Coexpression of miR-767-5p or depletion of TET2 rescued the inhibitory effect of LINC-PINT on thyroid cancer cell proliferation and invasion. In addition, there was a negative correlation between miR-767-5p and LINC-PINT in thyroid cancer (r = -0.34772, p = 0.01789). Taken together, LINC-PINT functions as a tumor suppressor in thyroid cancer via the miR-767-5p/TET2 axis, representing a potential therapeutic target for thyroid cancer.

引用

页码：319 / 328

页数：10

共 30 条

[1] TET2-Dependent Hydroxymethylome Plasticity Reduces Melanoma Initiation and Progression [J].

Bonvin, Elise ;

Radaelli, Enrico ;

Bizet, Martin ;

Luciani, Flavie ;

Calonne, Emilie ;

Putmans, Pascale ;

Nittner, David ;

Singh, Nitesh Kumar ;

Santagostino, Sara Francesca ;

Petit, Valerie ;

Larue, Lionel ;

Marine, Jean Christophe ;

Fuks, Francois .

CANCER RESEARCH, 2019, 79 (03) :482-494

[2] Molecular aspects of pancreatic β-cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA [J].

Borujeni, Mohammad Javad Saeedi ;

Esfandiary, Ebrahim ;

Baradaran, Azar ;

Valiani, Ali ;

Ghanadian, Mustafa ;

Codoner-Franch, Pilar ;

Basirat, Reyhane ;

Alonso-Iglesias, Eulalia ;

Mirzaei, Hamed ;

Yazdani, Amid .

JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (06) :8411-8425

[3] Thyroid cancer [J].

Cabanillas, Maria E. ;

McFadden, David G. ;

Durante, Cosimo .

LANCET, 2016, 388 (10061) :2783-2795

[4] Silencing of long noncoding RNA LINC00958 prevents tumor initiation of pancreatic cancer by acting as a sponge of microRNA-330-5p to down-regulate PAX8 [J].

Chen, Shi ;

Chen, Jiang-Zhi ;

Zhang, Jia-Qiang ;

Chen, Hui-Xing ;

Qiu, Fu-Nan ;

Yan, Mao-Lin ;

Tian, Yi-Feng ;

Peng, Cheng-Hong ;

Shen, Bai-Yong ;

Chen, Yan-Ling ;

Wang, Yao-Dong .

CANCER LETTERS, 2019, 446 :49-61

[5] An Extensive Network of TET2-Targeting MicroRNAs Regulates Malignant Hematopoiesis [J].

Cheng, Jijun ;

Guo, Shangqin ;

Chen, Suning ;

Mastriano, Stephen J. ;

Liu, Chaochun ;

D'Alessio, Ana C. ;

Hysolli, Eriona ;

Guo, Yanwen ;

Yao, Hong ;

Megyola, Cynthia M. ;

Li, Dan ;

Liu, Jun ;

Pan, Wen ;

Roden, Christine A. ;

Zhou, Xiao-Ling ;

Heydari, Kartoosh ;

Chen, Jianjun ;

Park, In-Hyun ;

Ding, Ye ;

Zhang, Yi ;

Lu, Jun .

CELL REPORTS, 2013, 5 (02) :471-481

[6] Immunity drives TET1 regulation in cancer through NF-κB [J].

Collignon, Evelyne ;

Canale, Annalisa ;

Al Wardi, Clemence ;

Bizet, Martin ;

Calonne, Emilie ;

Dedeurwaerder, Sarah ;

Garaud, Soizic ;

Naveaux, Celine ;

Barham, Whitney ;

Wilson, Andrew ;

Bouchat, Sophie ;

Hubert, Pascale ;

Van Lint, Carine ;

Yull, Fiona ;

Sotiriou, Christos ;

Willard-Gallo, Karen ;

Noel, Agnes ;

Fuks, Francois .

SCIENCE ADVANCES, 2018, 4 (06)

[7] Estrogen receptor β promotes renal cell carcinoma progression via regulating LncRNA HOTAIR-miR-138/200c/204/217 associated CeRNA network [J].

Ding, Jie ;

Yeh, Chiuan-Ren ;

Sun, Yin ;

Lin, Changyi ;

Chou, Joshua ;

Ou, Zhenyu ;

Chang, Chawnshang ;

Qi, Jun ;

Yeh, Shuyuan .

ONCOGENE, 2018, 37 (37) :5037-5053

[8] Long noncoding RNA LINC-PINT is inhibited in gastric cancer and predicts poor survival [J].

Feng, Hua ;

Zhang, Junyong ;

Shi, Yongjun ;

Wang, Lifen ;

Zhang, Chunqing ;

Wu, Lei .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2019, 120 (06) :9594-9600

[9] CircRNA circ_0000190 inhibits the progression of multiple myeloma through modulating miR-767-5p/MAPK4 pathway [J].

Feng, Yashu ;

Zhang, Ling ;

Wu, Jieying ;

Khadka, Bijay ;

Fang, Zhigang ;

Gu, Jiaming ;

Tang, Baoqiang ;

Xiao, Ruozhi ;

Pan, Guangjin ;

Liu, Jiajun .

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2019, 38 (1)

[10] MicroRNA-146b-5p as an oncomiR promotes papillary thyroid carcinoma development by targeting CCDC6 [J].

Jia, Meng ;

Shi, Yang ;

Li, Zhuyao ;

Lu, Xiubo ;

Wang, Jiaxiang .

CANCER LETTERS, 2019, 443 :145-156

← 1 2 3 →