Circular RNA hsa_circ_0006401 promotes proliferation and metastasis in colorectal carcinoma.
Circular RNA hsa_circ_0006401 promotes proliferation and metastasis in colorectal carcinoma.
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环状核糖核酸hsa_CIRC_0006401促进结直肠癌的增殖和转移
DOI：
10.1038/s41419-021-03714-8
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发表时间：
2021-05-04
影响因子：
9
通讯作者：
Pan W
中科院分区：
文献类型：
--
作者：
Zhang C;Zhou X;Geng X;Zhang Y;Wang J;Wang Y;Jing J;Zhou X;Pan W
环状RNA（circRNA）表达的失调参与癌症的进展。本文旨在研究hsa_circ_0006401在结直肠癌（CRC）中的潜在功能。通过实时定量PCR（qRT-PCR）和circRNA原位杂交（RNA-ISH）分析CRC和癌旁非肿瘤组织中circRNA hsa_circ_0006401的表达水平。然后，通过细胞计数评估CRC细胞增殖。利用伤口愈合和transwell测定来检测hsa_circ_0006401对CRC迁移的影响。创建circRNA-ORF构建体，并制备针对hsa_circ_0006401的剪接点的特异性抗体。最后，通过免疫沉淀结合质谱鉴定与hsa_circ_0006401肽直接结合的蛋白质。在我们的研究中，我们发现hsa_circ_0006401与结直肠癌转移密切相关，并且在转移性结直肠癌组织样品中表现出上调表达。当hsa_circ_0006401表达沉默时，体外增殖和迁移受到抑制。hsa_circ_0006401表达下调可降低体内CRC增殖和肝转移。一个198个氨基酸的肽编码的剪接点的序列不存在的col 6a 3。Hsa_circ_0006401通过编码hsa_circ_0006401肽促进CRC增殖和迁移。Hsa_circ_0006401肽通过促进宿主基因col 6a 3 mRNA的稳定性而降低宿主基因col 6a 3的mRNA和蛋白水平。综上所述，我们的研究表明，从含有开放阅读框（ORF）的col 6a 3产生的circRNA编码新的198-aa功能肽，并且hsa_circ_0006401肽促进宿主基因col 6a 3 mRNA的稳定性以促进CRC增殖和转移。
Dysregulation of circular RNA (circRNA) expression is involved in the progression of cancer. Here, we aimed to study the potential function of hsa_circ_0006401 in colorectal cancer (CRC). CircRNA hsa_circ_0006401 expression levels in CRC and adjacent nontumor tissues were analyzed by real-time quantitative PCR (qRT-PCR) and circRNA in situ hybridization (RNA-ISH). Then, CRC cell proliferation was assessed by cell counting. Wound-healing and transwell assays were utilized to detect the effect of hsa_circ_0006401 on CRC migration. A circRNA-ORF construct was created, and a specific antibody against the splice junction of hsa_circ_0006401 was prepared. Finally, the proteins directly binding to hsa_circ_0006401 peptides were identified by immunoprecipitation combined with mass spectrometry. In our study, we found hsa_circ_0006401 was closely related to CRC metastasis and exhibited upregulated expression in metastatic CRC tissue samples. Proliferation and migration were inhibited in vitro when hsa_circ_0006401 expression was silenced. Downregulation of hsa_circ_0006401 expression decreased CRC proliferation and liver metastasis in vivo. A 198-aa peptide was encoded by sequences of the splice junction absent from col6a3. Hsa_circ_0006401 promoted CRC proliferation and migration by encoding the hsa_circ_0006401 peptide. Hsa_circ_0006401 peptides decreased the mRNA and protein level of the host gene col6a3 by promoting col6a3 mRNA stabilation. In conclusion, our study revealed that circRNAs generated from col6a3 that contain an open-reading frame (ORF) encode a novel 198-aa functional peptide and hsa_circ_0006401 peptides promote stability of the host gene col6a3 mRNA to promote CRC proliferation and metastasis.
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作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
16
作者：
Pamudurti NR;Bartok O;Jens M;Ashwal-Fluss R;Stottmeister C;Ruhe L;Hanan M;Wyler E;Perez-Hernandez D;Ramberger E;Shenzis S;Samson M;Dittmar G;Landthaler M;Chekulaeva M;Rajewsky N;Kadener S
通讯作者：
Kadener S