MiR-144-3p: a novel tumor suppressor targeting MAPK6 in cervical cancer
MiR-144-3p: a novel tumor suppressor targeting MAPK6 in cervical cancer
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DOI：
10.1007/s13105-019-00681-9
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发表时间：
2019-06-01
影响因子：
3.4
通讯作者：
Qiao, Baohua
中科院分区：
文献类型：
--
作者：
Wu, Jingli;Zhao, Yuying;Qiao, Baohua
宫颈癌是世界上第三大常见的妇科癌症。探索宫颈癌发病的分子机制将为开发新的治疗方法提供新的见解。在这项研究中，我们的目的是描述一种新的miRNA在宫颈癌肿瘤发生。首先，我们检测了miR-144- 3 p在临床组织和癌细胞中的表达变化。其次，我们采用细胞增殖、细胞迁移和侵袭试验来了解其在宫颈癌中的功能作用。然后，我们在异种移植癌症模型中证实了体外发现。最后，我们定位了miR-144- 3 p的下游靶点，并验证了其在癌细胞中的功能作用。结果发现miR-144- 3 p在宫颈癌细胞和组织中显著下调。过表达miR-144- 3 p抑制癌细胞生长和转移。与体外结果一致，过表达miR-144- 3 p导致体内肿瘤生长抑制。此外，MAPK 6被鉴定为宫颈癌中miR-144- 3 p的内源性靶标。敲低MAPK 6可抑制宫颈癌细胞的增殖、迁移和侵袭能力。我们的研究是第一次报道miR-144- 3 p作为宫颈癌中的肿瘤抑制miRNA。它通过靶向MAKP 6抑制肿瘤生长。新发现的信号传导轴可能作为新的治疗靶点来管理宫颈癌。
Cervical cancer is the third most common gynecologic cancer in the world. Exploration of the molecular mechanism underlying cervical cancer pathogenesis will provide new insights into the development of novel therapies. In this study, we were aimed to characterize a novel miRNA in cervical cancer tumorigenesis. First, we measured the expressional change of miR-144-3p in clinical tissues and cancer cells. Second, we employed cell proliferation, cell migration, and invasion assays to understand its functional role in cervical cancer. Then, we confirmed in vitro findings in xenograft cancer model. Last, we mapped out a downstream target of miR-144-3p and validated its functional role in cancer cells. In the results, miR-144-3p was found significantly downregulated in cervical cancer cells and tissues. Over-expressing miR-144-3p suppressed cancer cells growth and metastasis. Consistent with in vitro results, over-expressing miR-144-3p led to tumor growth inhibition in vivo. Further on, MAPK6 was identified as an endogenous target of miR-144-3p in cervical cancer. Knocking down MAPK6 inhibited cervical cancer cells proliferation, migration, and invasion potential. Our investigation was the first time to report miR-144-3p as a tumor suppressive miRNA in cervical cancer. It inhibited tumor growth by targeting MAKP6. The newly identified signalling axis may serve as novel therapeutic targets to manage cervical cancer.