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长链非编码 RNA-ENST00000501520 通过靶基因促进煤焦沥青诱导的恶性转化 BEAS-2B 细胞的增殖。

LncRNA-ENST00000501520 promotes the proliferation of malignant-transformed BEAS-2B cells induced with coal tar pitch mediated by target genes.

机构信息

Department of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.

Department of Bone and soft tissue cancer, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, Henan, China.

出版信息

Environ Toxicol. 2019 Jul;34(7):869-877. doi: 10.1002/tox.22759. Epub 2019 Apr 29.

Abstract

As a human carcinogen, coal tar pitch (CTP) can significantly increase the risk of lung cancer. However, the mechanism underlying CTP-induced lung carcinogenesis has not been well understood. This study aims to explore the role of the LncRNA-ENST00000501520 in the proliferation of malignant-transformed human bronchial epithelial cells (BAES-2B) induced by CTP extract for the first time. BEAS-2B cells were stimulated with 2.4 μg/mL CTP extract, and then passaged for three times, which were named passage 1 and then passaged until passage 30 (named as CTP group). The ENST000001520 of cells in CTP group was interfered using siRNA. The results showed that ENST000001520 located in cell nucleus (>80%) had no or weak ability of protein encoding. After interference of ENST000001520, the migration and proliferation of cells in CTP group were inhibited, and the cell cycle was arrested in the G0/G1 phase; however, the apoptosis of cells in CTP group was promoted. The target genes (SKB1, CLTB, TAP2, PIPK2, and SOCS3) of ENST000001520 were screened out, and the mRNA and protein expression of SBK1 and SOCS3 was significantly decreased after ENST000001520 interference. SBK1 and SOCS3 may play a promoting role in occurrence and development of cancers. The study suggests that LncRNA-ENST00000501520 could promote the proliferation in malignant-transformed BEAS-2B cells induced with CTP extract which may be mediated by target genes. This study may provide a new target for prevention and treatment of lung cancer.

摘要

作为一种人类致癌物质,煤焦油沥青(CTP)可显著增加肺癌风险。然而,CTP 诱导肺癌发生的机制尚未完全清楚。本研究旨在首次探讨 LncRNA-ENST00000501520 在 CTP 提取物诱导的恶性转化人支气管上皮细胞(BAES-2B)增殖中的作用。用 2.4μg/ml CTP 提取物刺激 BEAS-2B 细胞,然后传代 3 次,分别命名为第 1 代,然后传代至第 30 代(命名为 CTP 组)。用 siRNA 干扰 CTP 组细胞的 ENST000001520。结果表明,ENST000001520 位于细胞核中(>80%),几乎没有或弱的蛋白质编码能力。干扰 ENST000001520 后,CTP 组细胞的迁移和增殖受到抑制,细胞周期被阻滞在 G0/G1 期;然而,CTP 组细胞的凋亡被促进。筛选出 ENST000001520 的靶基因(SKB1、CLTB、TAP2、PIPK2 和 SOCS3),ENST000001520 干扰后 SKB1 和 SOCS3 的 mRNA 和蛋白表达明显下降。SKB1 和 SOCS3 可能在癌症的发生和发展中起促进作用。该研究表明,LncRNA-ENST00000501520 可促进 CTP 提取物诱导的恶性转化 BEAS-2B 细胞的增殖,其可能通过靶基因介导。本研究可为肺癌的防治提供新的靶点。

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