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

LINC-PINT Suppresses the Aggressiveness of Thyroid Cancer by Downregulating miR-767-5p to Induce TET2 Expression.
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LINC-PINT 通过下调 miR-767-5p 诱导 TET2 表达来抑制甲状腺癌的侵袭性

DOI:
10.1016/j.omtn.2020.05.033
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发表时间:
2020-12-04
期刊:
Molecular therapy. Nucleic acids
影响因子:
--
通讯作者:
Lu X
Lu X
中科院分区:
其他
文献类型:
--
作者:
Jia M;Li Z;Pan M;Tao M;Wang J;Lu X

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长链非编码RNA(lncRNA)长基因间非蛋白编码RNA,p53诱导转录物(LINC-PINT)在肺癌和结肠癌细胞中显示出抗侵袭活性。然而,LINC-PINT在甲状腺癌中的作用尚不清楚。在本工作中,我们探讨了LINC-PINT在60对甲状腺癌和癌旁正常组织中的表达。探讨LINC-PINT在甲状腺癌中的临床意义和生物学功能。LINC-PINT表达在甲状腺癌中相对于邻近正常组织下调(p = 0.0002)。LINC-PINT的低表达与晚期肿瘤淋巴结转移(TNM)分期(p = 0.0306)和淋巴结转移(p = 0.0359)显著相关。LINC-PINT的异位表达抑制甲状腺癌细胞的增殖、侵袭和肿瘤发生。在机制上,LINC-PINT与microRNA(miR)-767-5p相关并下调。此外,LINC-PINT过表达减轻了miR-767- 5 p介导的TET 2抑制。miR-767- 5 p促进甲状腺癌的侵袭性,这可被TET 2的过表达逆转。miR-767- 5 p的共表达或TET 2的消耗挽救了LINC-PINT对甲状腺癌细胞增殖和侵袭的抑制作用。此外,甲状腺癌中miR-767- 5 p和LINC-PINT之间存在负相关性(r =-0.34772,p = 0.01789)。总之,LINC-PINT通过miR-767- 5 p/TET 2轴作为甲状腺癌的肿瘤抑制因子发挥作用,代表了甲状腺癌的潜在治疗靶点。长链非编码RNA LINC-PINT在甲状腺癌中起肿瘤抑制作用。其下调有助于甲状腺癌的生长和进展。LINC-PINT的恢复为甲状腺癌提供了一种潜在的治疗策略。
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. Long noncoding RNA LINC-PINT functions as a tumor suppressor in thyroid cancer. Its downregulation contributes to thyroid cancer growth and progression. Restoration of LINC-PINT provides a potential therapeutic strategy against thyroid cancer.
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