Shen Xudong, Zhuang Zhixiang, Zhang Yusong, Chen Zhigang, Shen Liqin, Pu Wangyang, Chen Lei, Xu Zhonghua
Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Tumour Biol. 2015 Sep;36(9):7133-42. doi: 10.1007/s13277-015-3418-y. Epub 2015 Apr 16.
Although three therapeutic modalities (surgical resection, chemotherapy, and radiotherapy) have been established, long-term survival for lung cancer patients is still generally poor. Until now, the mechanisms of lung cancer genesis remain elusive. The JARID1B is a histone demethylase that has been proposed as oncogene in several types of human cancer, but its clinical significance and functional role in human non-small cell lung cancer (NSCLC) remain unclear. In present study, we found that JARID1B was overexpressed in lung cancer cell lines and lung cancer tissues but not in normal lung tissues. The proliferation and invasive potential of lung cancer cells was significantly increased by ectopic expression of JARID1B. Contrarily, RNA interference targeting JARID1B in lung cancer cells significantly decreased the proliferation and invasive potential of cells. Moreover, we also found that the expression of p53 was modulated by JARID1B. Overexpressed JARID1B cell exhibited greatly decreased p53 expression, whereas silencing of JARID1B expression dramatically increased p53 expression at both the messenger RNA (mRNA) and protein levels. Inhibition of p53 by small interfering RNA (siRNA) reversed the shJARID1B-induced suppression of proliferation and invasion. Our results collectively suggested that JARID1B expressed in lung cancer played a role in lung cancer cells proliferation and invasion, which may be partly associated with the p53 expression.
尽管已经确立了三种治疗方式（手术切除、化疗和放疗），但肺癌患者的长期生存率总体上仍然很低。到目前为止，肺癌发生的机制仍然不清楚。JARID1B是一种组蛋白去甲基化酶，在几种人类癌症中被认为是癌基因，但其在人类非小细胞肺癌（NSCLC）中的临床意义和功能作用仍不清楚。在本研究中，我们发现JARID1B在肺癌细胞系和肺癌组织中过表达，而在正常肺组织中不表达。JARID1B的异位表达显著增加了肺癌细胞的增殖和侵袭能力。相反，在肺癌细胞中靶向JARID1B的RNA干扰显著降低了细胞的增殖和侵袭能力。此外，我们还发现p53的表达受JARID1B调节。过表达JARID1B的细胞表现出p53表达大大降低，而沉默JARID1B表达则在信使RNA（mRNA）和蛋白质水平上显著增加p53表达。通过小干扰RNA（siRNA）抑制p53可逆转shJARID1B诱导的增殖和侵袭抑制。我们的结果共同表明，在肺癌中表达的JARID1B在肺癌细胞增殖和侵袭中起作用，这可能部分与p53表达有关。
