Histone demethylase JARID1B/KDM5B promotes aggressiveness of non-small cell lung cancer and serves as a good prognostic predictor.
Histone demethylase JARID1B/KDM5B promotes aggressiveness of non-small cell lung cancer and serves as a good prognostic predictor.
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DOI：
10.1186/s13148-018-0533-9
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发表时间：
2018-08-09
影响因子：
5.7
通讯作者：
Yeh CT
中科院分区：
文献类型：
--
作者：
Kuo KT;Huang WC;Bamodu OA;Lee WH;Wang CH;Hsiao M;Wang LS;Yeh CT
肺癌是全球癌症死亡的主要原因。最近，表观遗传失调已被称为促进肿瘤进展，因此可能是抗癌治疗的治疗靶点。JARID 1B是组蛋白去甲基化酶的一个成员，已发现其与某些癌症的肿瘤发生有关。然而，其在非小细胞肺癌（NSCLC）中的生物学作用在很大程度上仍不清楚。我们首先检测了JARID 1B在手术标本和6个NSCLC细胞系中的表达。然后，我们评估了72例NSCLC患者中JARID 1B表达与临床病理参数之间的关系，从而确定其预后意义。我们随后研究了JARID 1B在肿瘤发生中的功能作用，以验证其临床病理学意义。我们的研究结果表明，JARID 1B在非小细胞肺癌细胞中过表达，并且JARID 1B过表达与非小细胞肺癌患者的肿瘤大小、淋巴结转移、晚期和总生存率低相关。JARID 1B过表达导致细胞增殖和肿瘤球形成增加，并与癌症干细胞（CSC）和上皮间质转化（EMT）标志物的表达呈正相关，而c-Met信号通路积极参与。它还与顺铂和阿霉素的耐药性强度相关。相反，通过应用shRNA或JARID 1B抑制剂PBIT下调JARID 1B表达逆转了这些现象。JARID 1B通过与c-Met信号激活相关的多个生物学方面促进肿瘤侵袭性来预测NSCLC患者的预后，并且可以成为NSCLC的新的预后生物标志物和治疗靶点。本文的在线版本（10.1186/s13148-018-0533-9）包含补充材料，可供授权用户使用。
Lung cancer is the leading cause of cancer death worldwide. Recently, epigenetic dysregulation has been known to promote tumor progression and therefore may be a therapeutic target for anticancer therapy. JARID1B, a member of histone demethylases, has been found to be related to tumorigenesis in certain kinds of cancers. However, its biological roles in non-small cell lung cancer (NSCLC) remain largely unclear. We firstly examined the expression of JARID1B in surgical specimens and six NSCLC cell lines. Then, we evaluated the relationship between JARID1B expression and clinicopathologic parameters in 72 NSCLC patients, thereby established its prognostic importance. We subsequently studied the functional roles of JARID1B in tumorigenesis to verify its clinicopathologic significance. Our results showed that JARID1B was overexpressed in NSCLC cells and JARID1B overexpression was associated with tumor size, lymph node metastasis, advanced stages, and poor overall survival in NSCLC patients. JARID1B overexpression resulted in increased cell proliferation and formation of tumorspheres and correlated positively with the expression of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) markers, while the c-Met signaling pathway was actively involved. It also correlated with the strength of resistance to cisplatin and doxorubicin. On the contrary, downregulation of JARID1B expression by applying shRNA or JARID1B inhibitor PBIT reversed these phenomena. JARID1B worsens prognosis of NSCLC patients by promotion of tumor aggressiveness through multiple biological facets which were associated with activation of the c-Met signaling, and can be a novel prognostic biomarker and therapeutic target for NSCLC. The online version of this article (10.1186/s13148-018-0533-9) contains supplementary material, which is available to authorized users.
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影响因子：
4.8
作者：
Sayegh, Joyce;Cao, Jian;Yan, Qin
通讯作者：
Yan, Qin
影响因子：
50.3
作者：
Roesch A;Vultur A;Bogeski I;Wang H;Zimmermann KM;Speicher D;Körbel C;Laschke MW;Gimotty PA;Philipp SE;Krause E;Pätzold S;Villanueva J;Krepler C;Fukunaga-Kalabis M;Hoth M;Bastian BC;Vogt T;Herlyn M
通讯作者：
Herlyn M
影响因子：
9.7
作者：
Lin, Chun-Shu;Lin, Ying-Chin;Yeh, Chi-Tai
通讯作者：
Yeh, Chi-Tai
影响因子：
8
作者：
Dulak, A. M.;Gubish, C. T.;Stabile, L. P.;Henry, C.;Siegfried, J. M.
通讯作者：
Siegfried, J. M.
影响因子：
5.4
作者：
Kristensen, Line H.;Nielsen, Anders L.;Gajhede, Michael
通讯作者：
Gajhede, Michael