STAT3/miR-135b/NF-κB axis confers aggressiveness and unfavorable prognosis in non-small-cell lung cancer.
STAT3/miR-135b/NF-κB axis confers aggressiveness and unfavorable prognosis in non-small-cell lung cancer.
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STAT3/miR-135b/NF-κB 轴赋予非小细胞肺癌侵袭性和不良预后。
DOI：
10.1038/s41419-021-03773-x
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发表时间：
2021-05-14
影响因子：
9
通讯作者：
Wu Z
中科院分区：
文献类型：
--
作者：
Zhao J;Wang X;Mi Z;Jiang X;Sun L;Zheng B;Wang J;Meng M;Zhang L;Wang Z;Song J;Yuan Z;Wu Z
非小细胞肺癌（NSCLC）是世界范围内最常见的癌症之一，但有效的治疗方法有限。揭示潜在的病理和分子变化，以及机制，将改善治疗。失调的microRNAs （miRNAs）已被证明在包括NSCLC在内的各种癌症的发生和发展中发挥重要作用。在本文中，我们鉴定了microRNA-135b （miR-135b）是NSCLC中促进肿瘤的miRNA。我们发现miR-135b显著上调，其上调与NSCLC患者预后不良相关。miR-135b是非小细胞肺癌的独立预后因子。过表达miR-135b可显著促进NSCLC的侵袭性，在体外和体内均可增强细胞增殖、迁移、侵袭、抗凋亡和血管生成，而下调miR-135b则具有相反的作用。在机制上，我们的研究结果表明，miR-135b直接靶向去泛素酶CYLD的3 ' -未翻译区（UTR），从而调节泛素化和NF-κB信号的激活。此外，我们发现白细胞介素-6 (IL-6)/STAT3可以提高miR-135b的水平，并且STAT3直接结合miR-135b的启动子；因此，这些发现强调了IL-6/STAT3/miR-135b/NF-κB信号在非小细胞肺癌中新的正反馈回路，并提示miR-135b可能是非小细胞肺癌的潜在治疗靶点。
Non-small-cell lung cancer (NSCLC) is one of the most commonly diagnosed cancers worldwide but has limited effective therapies. Uncovering the underlying pathological and molecular changes, as well as mechanisms, will improve the treatment. Dysregulated microRNAs (miRNAs) have been proven to play important roles in the initiation and progression of various cancers, including NSCLC. In this manuscript, we identified microRNA-135b (miR-135b) as a tumor-promoting miRNA in NSCLC. We found that miR-135b was significantly upregulated and that its upregulation was associated with poor prognosis in NSCLC patients. miR-135b was an independent prognostic factor in NSCLC. Overexpressing miR-135b significantly promoted the aggressiveness of NSCLC, as evidenced by enhanced cell proliferation, migration, invasion, anti-apoptosis, and angiogenesis in vitro and in vivo, and knockdown of miR-135b had the opposite effects. Mechanistically, our results reveal that miR-135b directly targets the 3′-untranslated region (UTR) of the deubiquitinase CYLD, thereby modulating ubiquitination and activation of NF-κB signaling. Moreover, we found that interleukin-6 (IL-6)/STAT3 could elevate miR-135b levels and that STAT3 directly bound the promoter of miR-135b; thus, these findings highlight a new positive feedback loop of the IL-6/STAT3/miR-135b/NF-κB signaling in NSCLC and suggest that miR-135b could be a potential therapeutic target for NSCLC.
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DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
4.8
作者：
Mauro, Claudio;Pacifico, Francesco;Leonardi, Antonio
通讯作者：
Leonardi, Antonio
miR-135b 在乳腺癌中表达上调，通过调节 LATS2 促进细胞生长并破坏细胞周期
影响因子：
5.2
作者：
Hua, Kaiyao;Jin, Jiali;Fang, Lin
通讯作者：
Fang, Lin
影响因子：
16
作者：
Ea, CK;Deng, L;Chen, ZJJ
通讯作者：
Chen, ZJJ
影响因子：
56.9
作者：
Lee, EG;Boone, DL;Ma, A
通讯作者：
Ma, A