LINC01140 promotes the progression and tumor immune escape in lung cancer by sponging multiple microRNAs.
LINC01140 promotes the progression and tumor immune escape in lung cancer by sponging multiple microRNAs.
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LINC01140通过海绵多种microRNA促进肺癌的进展和肿瘤免疫逃逸
DOI：
10.1136/jitc-2021-002746
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发表时间：
2021-08
影响因子：
10.9
通讯作者：
Mi Y
中科院分区：
文献类型：
--
作者：
Xia R;Geng G;Yu X;Xu Z;Guo J;Liu H;Li N;Li Z;Li Y;Dai X;Luo Q;Jiang J;Mi Y
LINC 01140是一种长链非编码RNA，在多种肿瘤中高度表达，但其在肺癌进展和免疫逃逸中的生物学功能尚不清楚。在此，为了阐明LINC 01140的功能，收集了79对LC和癌旁组织。使用荧光原位杂交和qPCR分析测定LINC 01140表达水平。进行细胞计数试剂盒-8（CCK-8）测定和transwell测定。使用RNA免疫沉淀测定法证实microRNA（miRNA）和LINC 01140之间的相互作用。流式细胞术分析细胞因子诱导的杀伤（CIK）细胞表型。通过ELISA测定细胞因子分泌水平。通过测定乳酸脱氢酶释放来评估CIK细胞毒性。此外，使用异种移植肿瘤小鼠模型来揭示LINC 01140的体内功能。我们发现LINC 01140在人LC组织和细胞系中高度表达。高水平LINC 01140与LC患者的生存率相关。LINC 01140上调通过与miR-33 a-5 p和miR-33 b-5 p直接相互作用促进LC细胞的增殖、迁移和侵袭，从而促进c-Myc表达，并抑制顺铂诱导的细胞凋亡。在皮下肿瘤异种移植小鼠中，LINC 01140敲低显著降低肿瘤生长和肺转移。此外，LINC 01140直接抑制miR-377-3 p和miR-155-5 p表达水平，导致其共同下游靶点程序性死亡配体1（PD-L1）上调，这是LC免疫治疗中的关键靶点。值得注意的是，我们证明了LINC 01140敲低，沿着CIK给药，通过降低严重联合免疫缺陷小鼠中PD-L1表达来抑制皮下LC异种移植物的生长。总之，LINC 01140过表达保护c-Myc和PD-L1 mRNA免受miRNA介导的抑制，并有助于LC细胞的增殖、迁移、侵袭和免疫逃逸。这些结果为LINC 01140作为LC治疗靶点提供了理论依据。
Long intergenic non-protein coding RNA 1140 (LINC01140), a long non-coding RNA, is highly expressed in various cancers; however, its biological functions in lung cancer (LC) progression and immune escape are still unclear. Here, to elucidate LINC01140 function, 79 paired LC and paracancerous tissues were collected. LINC01140 expression levels were determined using fluorescence in situ hybridization and qPCR analysis. Cell counting kit-8 (CCK-8) assay and transwell assays were performed. The interaction between microRNAs (miRNAs) and LINC01140 was confirmed using an RNA immunoprecipitation assay. Cytokine-induced killer (CIK) cell phenotypes were analyzed by flow cytometry. Cytokine secretion levels were determined by ELISA. CIK cytotoxicity was assessed by measuring lactate dehydrogenase release. Besides, xenograft tumor mouse models were used to unveil the in vivo function of LINC01140. We found that LINC01140 was highly expressed in human LC tissues and cell lines. High LINC01140 levels were associated with poor survival in patients with LC. LINC01140 upregulation promoted the proliferation, migration, and invasion of LC cells through direct interaction with miR-33a-5p and miR-33b-5p, thereby contributing to c-Myc expression and also inhibited cisplatin-induced cell apoptosis. In subcutaneous tumor xenograft mice, LINC01140 knockdown markedly reduced tumor growth and lung metastasis. Additionally, LINC01140 directly repressed miR-377-3 p and miR-155-5 p expression levels, resulting in the upregulation of their common downstream target programmed death-ligand 1 (PD-L1), a crucial target in LC immunotherapy. Notably, we proved that LINC01140 knockdown, along with CIK administration, suppressed the growth of subcutaneous LC xenografts by decreasing PD-L1 expression in severe combined immunodeficient mice. Taken together, LINC01140 overexpression protects c-Myc and PD-L1 mRNA from miRNA-mediated inhibition and contributes to the proliferation, migration, invasion, and immune escape of LC cells. These results provide a theoretical basis that LINC01140 is a promising target for LC treatment.
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SQSTM1/p62的上调有助于镍诱导的人支气管上皮细胞的恶性转化
影响因子：
13.3
作者：
Huang H;Zhu J;Li Y;Zhang L;Gu J;Xie Q;Jin H;Che X;Li J;Huang C;Chen LC;Lyu J;Gao J;Huang C
通讯作者：
Huang C
影响因子：
44.1
作者：
Liu Y;Lv J;Liu J;Li M;Xie J;Lv Q;Deng W;Zhou N;Zhou Y;Song J;Wang P;Qin C;Tong WM;Huang B
通讯作者：
Huang B
DOI：
10.1126/science.aac9935
发表时间：
2016-04-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Casey SC;Tong L;Li Y;Do R;Walz S;Fitzgerald KN;Gouw AM;Baylot V;Gütgemann I;Eilers M;Felsher DW
通讯作者：
Felsher DW
影响因子：
64.8
作者：
O'Donnell, KA;Wentzel, EA;Mendell, JT
通讯作者：
Mendell, JT
影响因子：
64.5
作者：
Kopp F;Mendell JT
通讯作者：
Mendell JT