长链非编码RNA MALAT1通过作为骨肉瘤细胞中miR-144-3p的竞争性内源RNA促进转移和增殖。
Long non-coding RNA MALAT1 for promoting metastasis and proliferation by acting as a ceRNA of miR-144-3p in osteosarcoma cells.
作者信息
Wang Yong, Zhang Yueyang, Yang Tao, Zhao Wei, Wang Ningning, Li Pengcheng, Zeng Xiandong, Zhang Weiguo
机构信息
The 4th Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, P. R. China.
Department of Pathology, Liaoning Cancer Hospital & Institute, Shenyang, P. R. China.
出版信息
Oncotarget. 2017 Jul 31;8(35):59417-59434. doi: 10.18632/oncotarget.19727. eCollection 2017 Aug 29.
Long non-coding RNAs (lncRNAs) are involved in various biological processes and diseases including osteosarcoma. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overly expressed in osteosarcoma. But the function and mechanism it works on in osteosarcoma proliferation and metastasis mediated by Rho associated coiled-coil containing protein kinase 1 (ROCK1) and Rho associated coiled-coil containing protein kinase 2 (ROCK2) remain unclear. In the present study, an elevated MALAT1 was found in osteosarcoma tissues and cell lines, and the elevated MALAT1 was correlated with a poor prognosis in osteosarcoma patients. The functional experiments show that a decreased MALAT1 could remarkably inhibit osteosarcoma cell metastasis and proliferation but induce cell cycle arrest, indicating that MALAT1 functioned as an oncogene in osteosarcoma. Furthermore, we confirmed that MALAT1 and ROCK1/ROCK2 which were targeted by microRNA-144-3p (miR-144-3p) shared the same miR-144-3p combining site. Furthermore, the constructed luciferase assay verified that MALAT1 was a target of miR-144-3p. Additionally, the results of a qRT-PCR demonstrated that MALAT1 and miR-144-3p repressed each other's expression in a reciprocal manner. Finally, we affirmed that an overexpression of MALAT1 inhibited ROCK1/ROCK2 expression and its mediated metastasis and proliferation by working as a competitive endogenous RNA (ceRNA) via miR-144-3p. In summary, the findings of this study based on the ceRNA theory, combining the research foundation of miR-144-3p, ROCK1 and ROCK2, taking MALAT1 as a new point of study, provided new insights into molecular level proliferation reversal and metastasis of osteosarcoma.
长链非编码RNA(lncRNAs)参与包括骨肉瘤在内的各种生物学过程和疾病。长链非编码RNA转移相关肺腺癌转录本1(MALAT1)在骨肉瘤中过度表达。但其在由含Rho相关卷曲螺旋蛋白激酶1(ROCK1)和含Rho相关卷曲螺旋蛋白激酶2(ROCK2)介导的骨肉瘤增殖和转移中的作用及机制仍不清楚。在本研究中,发现骨肉瘤组织和细胞系中MALAT1水平升高,且MALAT1升高与骨肉瘤患者预后不良相关。功能实验表明,MALAT1水平降低可显著抑制骨肉瘤细胞转移和增殖,但诱导细胞周期停滞,表明MALAT1在骨肉瘤中起癌基因作用。此外,我们证实MALAT1和受微小RNA-144-3p(miR-144-3p)靶向的ROCK1/ROCK2共享相同的miR-144-3p结合位点。此外,构建的荧光素酶报告基因检测证实MALAT1是miR-144-3p的靶标。另外,qRT-PCR结果表明MALAT1和miR-144-3p以相互的方式抑制彼此的表达。最后,我们证实MALAT1过表达通过作为miR-144-3p的竞争性内源RNA(ceRNA)抑制ROCK1/ROCK2表达及其介导的转移和增殖。总之,本研究基于ceRNA理论的发现,结合miR-144-3p、ROCK1和ROCK2的研究基础,以MALAT1作为新的研究点,为骨肉瘤分子水平的增殖逆转和转移提供了新的见解。
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