癌症研究
生物
转移
级联
MAPK/ERK通路
选择性拼接
RNA剪接
化学
细胞生物学
癌症
信号转导
外显子
核糖核酸
遗传学
基因
色谱法
作者
Quanli Zhang,Limin Zheng,Yongkang Bai,Chi Su,Yongzhe Che,Jiawen Xu,Kemin Sun,Jie Ni,Lingli Huang,Shen Ye,Lili Jia,Lin Xu,Rong Yin,Ming Li,Jingwen Hu
出处
期刊:Cancer Letters
[Elsevier]
日期:2023-11-01
卷期号:577: 216426-216426
被引量:2
标识
DOI:10.1016/j.canlet.2023.216426
摘要
The mechanisms underlying the involvement of long non-coding RNAs (lncRNAs) in the metastasis of small cell lung cancer (SCLC) remain largely unknown. Here, we identified that the lncRNA ITPR1-AS1 was upregulated in SCLC and lymph node metastasis tissues and positively correlated with SCLC malignant features. The overexpression of ITPR1-AS1 in SCLC was an independent risk factor for the overall survival of patients with SCLC. Our data confirmed that ITPR1-AS1 induces SCLC cell metastasis both in vitro and in vivo. Mechanistically, ITPR1-AS1 acts as a scaffold to enhance the interaction between SRC-associated in mitosis 68 kDa and heterogeneous nuclear ribonucleoprotein A1, which facilitates the alternative splicing of the H-Ras proto-oncogene (HRAS) pre-mRNA (P21HRAS). Moreover, we observed that ITPR1-AS1 could associate in a complex with and maintain the stability of DEAD-box polypeptide 3 (DDX3X), which inhibited the latter’s ubiquitination and degradation. Our data provide evidence that ITPR1-AS1 activates the cRaf-MEK-ERK cascade by upregulating P21HRAS production and stabilizing DDX3X, to promote SCLC metastasis.
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