Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer.
Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer.
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环状RNA circHERC4作为一种新型致癌驱动因素，通过miR-556-5p/CTBP2/E-钙粘蛋白轴促进结直肠癌肿瘤转移
DOI：
10.1186/s13045-021-01210-2
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发表时间：
2021-11-15
影响因子：
28.5
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
He J;Chu Z;Lai W;Lan Q;Zeng Y;Lu D;Jin S;Xu H;Su P;Yin D;Chu Z;Liu L
结直肠癌患者死亡的主要原因是转移。越来越多的证据表明circRNA在肿瘤的发生和发展中起着关键作用。然而，协调癌症转移的circRNA的潜在分子机制仍然模糊，需要进一步澄清。使用两对CRC和相邻正常组织，通过circRNA-seq筛选上调的circRNA;然后，应用细胞侵袭试验来确认功能性侵袭相关的circRNA。根据上述方法，选择circHERC 4（hsa_circ_0007113）进行进一步研究。接下来，我们在一个大型CRC患者队列中研究了circHERC 4的临床意义。在CRC细胞系和动物异种移植研究中研究了circHERC 4的致癌活性。最后，我们探索了circHERC 4作为恶性驱动因素的分子机制。我们发现circHERC 4在结直肠癌组织中异常升高（P < 0.001），并且与淋巴结转移和肿瘤的晚期分级正相关（P < 0.01）。值得注意的是，circHERC 4的表达与CRC患者的生存率较差相关。circHERC 4的沉默显著抑制了两种高度侵袭性CRC细胞系的增殖和迁移，并减少了体内肝和肺转移。从机制上讲，我们揭示了circHERC 4使肿瘤抑制因子miR-556- 5 p失活，导致CTBP 2/E-cadherin途径激活，从而促进CRC中的肿瘤转移。CircHERC 4通过miR-556- 5 p/CTBP 2/E-cadherin途径在促进肿瘤侵袭性中发挥关键作用，并且是疾病的预后生物标志物，表明circHERC 4可以作为CRC患者的可开发的治疗靶点。在线版本包含补充材料，可通过10.1186/s13045-021-01210-2获得。
The main cause of death in colorectal cancer patients is metastasis. Accumulating evidences suggest that circRNA plays pivotal roles in cancer initiation and development. However, the underlying molecular mechanisms of circRNAs that orchestrate cancer metastasis remain vague and need further clarification. Two paired CRC and adjacent normal tissues were used to screen the upregulated circRNAs by circRNA-seq; then, cell invasion assay was applied to confirm the functional invasion-related circRNAs. According to the above methods, circHERC4 (hsa_circ_0007113) was selected for further research. Next, we investigated the clinical significance of circHERC4 in a large cohort of patients with CRC. The oncogenic activity of circHERC4 was investigated in both CRC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying circHERC4 as a malignant driver. We demonstrated that circHERC4 was aberrantly elevated in CRC tissues (P < 0.001), and was positively associated with lymph node metastasis and advanced tumor grade (P < 0.01). Notably, the expression of circHERC4 was associated with worse survival in patients with CRC. Silencing of circHERC4 significantly inhibited the proliferation and migration of two highly aggressive CRC cell lines and reduced liver and lung metastasis in vivo. Mechanistically, we revealed that circHERC4 inactivated the tumor suppressor, miR-556-5p, leading to the activation of CTBP2/E-cadherin pathway which promotes tumor metastasis in CRC. CircHERC4 exerts critical roles in promoting tumor aggressiveness through miR-556-5p/CTBP2/E-cadherin pathway and is a prognostic biomarker of the disease, suggesting that circHERC4 may serve as an exploitable therapeutic target for patients with CRC. The online version contains supplementary material available at 10.1186/s13045-021-01210-2.
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DOI：
10.1007/s00018-017-2688-5
发表时间：
2018-03
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Holdt LM;Kohlmaier A;Teupser D
通讯作者：
Teupser D
DOI：
10.1126/science.abc9359
发表时间：
2020-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Shi CY;Kingston ER;Kleaveland B;Lin DH;Stubna MW;Bartel DP
通讯作者：
Bartel DP
影响因子：
10.9
作者：
Dong B;Li S;Zhu S;Yi M;Luo S;Wu K
通讯作者：
Wu K
DOI：
10.1073/pnas.0830998100
发表时间：
2003-04-15
影响因子：
11.1
作者：
Grooteclaes, M;Deveraux, Q;Frisch, SM
通讯作者：
Frisch, SM
Hsa_circ_0009361 作为 miR-582 的海绵，通过调节 APC2 表达抑制结直肠癌进展
影响因子：
6
作者：
Geng, Yiting;Zheng, Xiao;Jiang, Jingting
通讯作者：
Jiang, Jingting