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沉默长链非编码 RNA DLX6-AS1 或恢复 microRNA-193b-3p 通过抑制 HOXA1 增强甲状腺癌细胞自噬和凋亡。

Silencing long non-coding RNA DLX6-AS1 or restoring microRNA-193b-3p enhances thyroid carcinoma cell autophagy and apoptosis via depressing HOXA1.

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing, China.

出版信息

J Cell Mol Med. 2021 Oct;25(19):9319-9330. doi: 10.1111/jcmm.16868. Epub 2021 Sep 12.

Abstract

Long non-coding RNA DLX6 antisense RNA 1 (DLX6-AS1) lists a critical position in thyroid carcinoma (TC) development. However, the overall comprehension about DLX6-AS1, microRNA (miR)-193b-3p and homeobox A1 (HOXA1) in TC is not thoroughly enough. Concerning to this, this work is pivoted on DLX6-AS1/miR-193b-3p/HOXA1 axis in TC cell growth and autophagy. TC tissues and adjacent normal thyroid tissues were collected, in which expression of DLX6-AS1, miR-193b-3p and HOXA1 was tested, together with their interactions. TC cells were transfected with DLX6-AS1/miR-193b-3p-related oligonucleotides or plasmids to test cell growth and autophagy. Tumorigenesis in nude mice was observed. DLX6-AS1 and HOXA1 were up-regulated, and miR-193b-3p was down-regulated in TC. Depleted DLX6-AS1 or restored miR-193b-3p disturbed cell growth and promoted autophagy. DLX6-AS1 targeted miR-193b-3p and positively regulated HOXA1. miR-193b-3p inhibition mitigated the impaired tumorigenesis induced by down-regulated DLX6-AS1. Tumorigenesis in nude mice was consistent with that in cells. It is clear that DLX6-AS1 depletion hinders TC cell growth and promotes autophagy via up-regulating miR-193b-3p and down-regulating HOXA1.

摘要

长链非编码 RNA DLX6 反义 RNA 1(DLX6-AS1)在甲状腺癌(TC)发展中起着关键作用。然而,人们对 TC 中 DLX6-AS1、微小 RNA(miR)-193b-3p 和同源盒 A1(HOXA1)的整体认识还不够全面。有鉴于此,本研究主要关注 TC 细胞生长和自噬中的 DLX6-AS1/miR-193b-3p/HOXA1 轴。收集 TC 组织和相邻正常甲状腺组织,检测 DLX6-AS1、miR-193b-3p 和 HOXA1 的表达及其相互作用。用 DLX6-AS1/miR-193b-3p 相关寡核苷酸或质粒转染 TC 细胞,检测细胞生长和自噬。观察裸鼠的致瘤性。TC 中 DLX6-AS1 和 HOXA1 上调,miR-193b-3p 下调。DLX6-AS1 耗竭或恢复 miR-193b-3p 扰乱细胞生长并促进自噬。DLX6-AS1 靶向 miR-193b-3p 并正向调节 HOXA1。miR-193b-3p 抑制减轻了下调的 DLX6-AS1 引起的肿瘤发生受损。裸鼠的肿瘤发生与细胞一致。显然,DLX6-AS1 耗竭通过上调 miR-193b-3p 和下调 HOXA1 来阻碍 TC 细胞生长并促进自噬。

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