Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling.
Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling.
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DOI：
10.1038/s41419-020-03316-w
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发表时间：
2021-01-04
影响因子：
9
通讯作者：
Jiang J
中科院分区：
文献类型：
--
作者：
Wang J;He Z;Xu J;Chen P;Jiang J
越来越多的证据表明长链非编码RNA参与了胰腺癌的发生和发展。在这项研究中，我们研究了LINC 00941在PC中的功能和分子作用机制。采用定量PCR检测LINC 00941和miR-335- 5 p在PC组织和细胞系中的表达，并探讨LINC 00941表达与PC临床病理特征的相关性。使用质粒载体或慢病毒操纵PC细胞系中LINC 00941、miR-335- 5 p和ROCK 1的表达。采用功能获得或丧失测定和机制测定来验证LINC 00941、miR-335- 5 p和ROCK 1在体内和体外PC细胞生长和转移中的作用。发现LINC 00941和ROCK 1在PC中高表达，而miR-335- 5 p表现出低表达。LINC 00941高表达与肿瘤较大、淋巴结转移和预后不良密切相关。功能实验显示LINC 00941沉默显著抑制PC细胞生长、转移和上皮-间充质转化。LINC 00941作为miR-335- 5 p的分子海绵和ROCK 1的竞争性内源RNA（ceRNA）发挥作用，促进ROCK 1上调和LIMK 1/Cofilin-1通路激活。我们的观察使我们得出结论，LINC 00941在PC进展中作为癌基因发挥作用，表现为miR-335- 5 p结合的ceRNA。因此，LINC 00941可能具有作为该疾病的诊断和治疗靶点的潜在效用。
An accumulation of evidence indicates that long noncoding RNAs are involved in the tumorigenesis and progression of pancreatic cancer (PC). In this study, we investigated the functions and molecular mechanism of action of LINC00941 in PC. Quantitative PCR was used to examine the expression of LINC00941 and miR-335-5p in PC tissues and cell lines, and to investigate the correlation between LINC00941 expression and clinicopathological features. Plasmid vectors or lentiviruses were used to manipulate the expression of LINC00941, miR-335-5p, and ROCK1 in PC cell lines. Gain or loss-of-function assays and mechanistic assays were employed to verify the roles of LINC00941, miR-335-5p, and ROCK1 in PC cell growth and metastasis, both in vivo and in vitro. LINC00941 and ROCK1 were found to be highly expressed in PC, while miR-335-5p exhibited low expression. High LINC00941 expression was strongly associated with larger tumor size, lymph node metastasis, and poor prognosis. Functional experiments revealed that LINC00941 silencing significantly suppressed PC cell growth, metastasis and epithelial–mesenchymal transition. LINC00941 functioned as a molecular sponge for miR-335-5p, and a competitive endogenous RNA (ceRNA) for ROCK1, promoting ROCK1 upregulation, and LIMK1/Cofilin-1 pathway activation. Our observations lead us to conclude that LINC00941 functions as an oncogene in PC progression, behaving as a ceRNA for miR-335-5p binding. LINC00941 may therefore have potential utility as a diagnostic and treatment target in this disease.
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影响因子：
8
作者：
Zhou Y;Huang T;Zhang J;Wong CC;Zhang B;Dong Y;Wu F;Tong JHM;Wu WKK;Cheng ASL;Yu J;Kang W;To KF
通讯作者：
To KF
DOI：
10.1016/j.pan.2016.12.010
发表时间：
2017-01
期刊：
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
影响因子：
--
作者：
Dauer P;Nomura A;Saluja A;Banerjee S
通讯作者：
Banerjee S
影响因子：
4
作者：
Liu R;Guo H;Lu S
通讯作者：
Lu S
影响因子：
28.2
作者：
Karreth FA;Pandolfi PP
通讯作者：
Pandolfi PP
长非编码RNA DANCR作为竞争性内源RNA，通过诱骗骨肉瘤中的miR-335-5p和miR-1972促进ROCK1介导的增殖和转移
影响因子：
37.3
作者：
Wang Y;Zeng X;Wang N;Zhao W;Zhang X;Teng S;Zhang Y;Lu Z
通讯作者：
Lu Z