m6 RNA甲基化调节因子KIAA1429与肺癌自噬介导的耐药性有关

IF 2.5 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bo Ma, Lei Xiu, Lili Ding
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引用次数: 0

摘要

N6-甲基腺苷(m6A)修饰在癌症进展中起着至关重要的作用。然而,m6A修饰介导的自噬在非小细胞肺癌(NSCLC)吉非替尼耐药中的基础作用仍然未知。在这里,我们发现m6A甲基转移酶KIAA1429在NSCLC吉非替尼耐药细胞(PC9-GR)和组织中高表达,而且KIAA1429的高表达与生存率低有关。此外,沉默的KIAA1429可抑制NSCLC的吉非替尼耐药性,并减少体内肿瘤的生长。从机理上讲,KIAA1429通过与WTAP的3′非翻译区(3′-UTR)结合,稳定了自噬中的重要角色WTAP。总之,我们的研究结果表明,KIAA1429能提高NSCLC吉非替尼的耐药性,这或许能为NSCLC患者提供一种前景广阔的靶向疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The m6 RNA methylation regulator KIAA1429 is associated with autophagy-mediated drug resistance in lung cancer

The m6 RNA methylation regulator KIAA1429 is associated with autophagy-mediated drug resistance in lung cancer

N6-methyladenosine (m6A) modification plays a crucial role in cancer progression. However, the role of m6A modification-mediated autophagy underlying non-small cell lung cancer (NSCLC) gefitinib resistance remains unknown. Here, we discovered that m6A methyltransferase KIAA1429 was highly expressed in NSCLC gefitinib-resistant cells (PC9-GR) as well as tissues, and KIAA1429 high expression was associated with poor survival. In addition, silent KIAA1429 repressed gefitinib resistance in NSCLC and reduced tumor growth in vivo. Mechanistically, KIAA1429 stabilized WTAP, a significant player in autophagy, by binding to the 3′ untranslated regions (3′-UTR) of WTAP. In a word, our findings indicated that KIAA1429 could elevate NSCLC gefitinib resistance, which may provide a promising targeted therapy for NSCLC patients.

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来源期刊
FASEB bioAdvances
FASEB bioAdvances Multiple-
CiteScore
5.40
自引率
3.70%
发文量
56
审稿时长
10 weeks
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