Wu Dejun, Li Yuqin, Xu Anjun, Tang Wenqing, Yu Bo
Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Shanghai 201399, China.
Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Shanghai 201399, China.
Cancers (Basel). 2023 Mar 30;15(7):2068. doi: 10.3390/cancers15072068.
Circular RNAs (circRNAs) have been shown to play a crucial role in cancer occurrence and progression. This present work investigated the link between hsa_circ_0008234 and colon cancer. Data retrieved from GSE172229 was used to compare the circRNA profiles of colon cancer and surrounding non-tumorous tissues. The amount of RNA and protein in the molecules was determined using quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The cell proliferation ability was assessed using CCK8, EdU, colon formation, and nude mice tumorigenesis tests. Cell invasion and migration abilities were evaluated using transwell wound healing and mice lung metastasis model. Hsa_circ_0008234 piqued our interest because bioinformatics and qRT-PCR analyses revealed that it is upregulated in colon cancer tissue. Cell phenotypic studies suggest that hsa_circ_0008234 may significantly increase colon cancer cell aggressiveness. Mice experiments revealed that inhibiting hsa_circ_0008234 significantly reduced tumor growth and metastasis. Moreover, the fluorescence in situ hybridization experiment demonstrated that hsa_circ_0008234 is primarily found in the cytoplasm, implying that it potentially functions via a competitive endogenous RNA pathway. These findings indicated that hsa_circ_0008234 may act as a "molecular sponge" for miR-338-3p, increasing the expression of miR-338-target 3p's ETS1. In addition, the traditional oncogenic pathway PI3K/AKT/mTOR signaling was found to be the potential downstream pathway of the hsa_circ_0008234/miR-338-3p/ETS1 axis. In conclusion, hsa_circ_0008234 increases colon cancer proliferation, infiltration, and migration via the miR-338-3p/ETS1/PI3K/AKT axis; therefore, it could serve as a target and a focus for colon cancer therapy.
环状RNA（circRNAs）已被证明在癌症的发生和发展中起关键作用。本研究调查了hsa_circ_0008234与结肠癌之间的联系。从GSE172229检索到的数据用于比较结肠癌组织和周围非肿瘤组织的环状RNA谱。分别使用定量实时PCR（qRT-PCR）和蛋白质免疫印迹分析来测定分子中的RNA和蛋白质含量。使用CCK8、EdU、结肠形成和裸鼠肿瘤发生试验评估细胞增殖能力。使用Transwell伤口愈合试验和小鼠肺转移模型评估细胞侵袭和迁移能力。hsa_circ_0008234引起了我们的兴趣，因为生物信息学和qRT-PCR分析显示它在结肠癌组织中上调。细胞表型研究表明，hsa_circ_0008234可能会显著增加结肠癌细胞的侵袭性。小鼠实验表明，抑制hsa_circ_0008234可显著降低肿瘤生长和转移。此外，荧光原位杂交实验表明，hsa_circ_0008234主要存在于细胞质中，这意味着它可能通过竞争性内源RNA途径发挥作用。这些发现表明，hsa_circ_0008234可能作为miR-338-3p的“分子海绵”，增加miR-338-3p靶标的ETS1的表达。此外，传统的致癌途径PI3K/AKT/mTOR信号通路被发现是hsa_circ_0008234/miR-338-3p/ETS1轴的潜在下游途径。总之，hsa_circ_0008234通过miR-338-3p/ETS1/PI3K/AKT轴增加结肠癌的增殖、浸润和迁移；因此，它可以作为结肠癌治疗的靶点和重点。
