hsa_circ_0003410 promotes hepatocellular carcinoma progression by increasing the ratio of M2/M1 macrophages through the miR-139-3p/CCL5 axis.
hsa_circ_0003410 promotes hepatocellular carcinoma progression by increasing the ratio of M2/M1 macrophages through the miR-139-3p/CCL5 axis.
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hsa_circ_0003410 通过 miR-139-3p/CCL5 轴增加 M2/M1 巨噬细胞的比例促进肝细胞癌进展
DOI：
10.1111/cas.15238
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发表时间：
2022-03
期刊：
影响因子：
5.7
通讯作者：
Xue X
中科院分区：
文献类型：
--
作者：
Cao P;Ma B;Sun D;Zhang W;Qiu J;Qin L;Xue X
非编码rna已被证实可以调节巨噬细胞的浸润，从而加速肿瘤的生物学进展，然而环状rna在肝细胞癌（HCC）中对巨噬细胞的调控尚不清楚。通过高通量RNA测序，我们证实hsa_circ_0003410在HCC中明显上调。5‐乙炔‐2′‐脱氧尿苷和transwell实验表明，hsa_circ_0003410促进了肝癌细胞的体外增殖和迁移。我们敲除了hsa_circ_0003410在HepG2细胞中的表达，并进行了下一代测序以确定hsa_circ_0003410可能的靶基因。京都基因与基因组百科分析显示，不同的基因主要富集于免疫相关通路。从机制上，我们确定CCL5是hsa_circ_0003410的靶基因。RNA‐FISH显示hsa_circ_0003410和CCL5的共表达。Western blot和ELISA也证实hsa_circ_0003410可以上调CCL5蛋白的表达。流式细胞术和免疫荧光检测显示，CCL5激活和募集M2巨噬细胞，增加M2/M1巨噬细胞的比例，促进HCC的进展。体外动物实验也证实了我们的结果。综上所述，我们的实验揭示了非编码rna在HCC微环境中起着关键作用，可以被认为是HCC诊断和预后的标志物。通过高通量测序，我们发现hsa_circ_0003410在HCC中显著过表达。我们证实hsa_circ_0003410可以通过海绵miR‐139‐3p促进CCL5的表达。流式细胞术发现CCL5能显著促进M2巨噬细胞的极化和募集，增加M2/M1巨噬细胞的比例。
Noncoding RNAs have been verified to regulate the infiltration of macrophages to accelerate tumor biological progression, however the regulation of macrophages by circular RNAs in hepatocellular carcinoma (HCC) remains unresolved. Using high‐throughput RNA sequencing, we demonstrated that hsa_circ_0003410 was clearly upregulated in HCC. 5‐Ethynyl‐2′‐deoxyuridine and transwell assays showed that hsa_circ_0003410 facilitated the proliferation and migration of HCC cells in vitro. We knocked down the expression of hsa_circ_0003410 in HepG2 cells and performed next‐generation sequencing to determine possible target genes of hsa_circ_0003410. Kyoto Encyclopedia of Genes and Genomes analysis revealed that different genes were mainly enriched in immune‐related pathways. Mechanistically, we identified CCL5 as the target gene of hsa_circ_0003410. RNA‐FISH showed the co‐expression of hsa_circ_0003410 and CCL5. Western blot and ELISA also verified that hsa_circ_0003410 could upregulate the expression of CCL5 protein. Flow cytometry and immunofluorescence assays indicated that CCL5 activated and recruited M2 macrophages and increased the ratio of M2/M1 macrophages to promote the progression of HCC. Animal experiments in vitro also confirmed our results. Taken together, our experiments revealed that noncoding RNAs play a critical role in the HCC microenvironment and can be considered as markers for the diagnosis and prognosis of HCC. Through high‐throughput sequencing, we found that hsa_circ_0003410 was significantly overexpressed in HCC. We verified that hsa_circ_0003410 could promote the expression of CCL5 by sponging miR‐139‐3p. Flow cytometry found that CCL5 could significantly promote the polarization and recruitment of M2 macrophages and increase the ratio of M2/M1 macrophages.
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影响因子：
8.7
作者：
Liu D;Mewalal R;Hu R;Tuskan GA;Yang X
通讯作者：
Yang X
circ-Sirt1 通过序列特异性相互作用控制 NF-B 激活，并通过与血管平滑肌细胞中的 miR-132/212 结合增强 SIRT1 表达
影响因子：
14.9
作者：
Kong, Peng;Yu, Yuan;Han, Mei
通讯作者：
Han, Mei
DOI：
10.1016/j.bbrc.2009.07.035
发表时间：
2009-09-18
影响因子：
3.1
作者：
Murooka, Thomas T.;Rahbar, Ramtin;Fish, Eleanor N.
通讯作者：
Fish, Eleanor N.
DOI：
10.1126/science.aad4076
发表时间：
2016-01-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nelson BR;Makarewich CA;Anderson DM;Winders BR;Troupes CD;Wu F;Reese AL;McAnally JR;Chen X;Kavalali ET;Cannon SC;Houser SR;Bassel-Duby R;Olson EN
通讯作者：
Olson EN
影响因子：
25.7
作者：
Mohs, Antje;Kuttkat, Nadine;Trautwein, Christian
通讯作者：
Trautwein, Christian