Gastrointestinal Surgery, Wuhan Union Hospital, Wuhan, China.
Genet Res (Camb). 2022 Mar 14;2022:4237327. doi: 10.1155/2022/4237327. eCollection 2022.
Colorectal cancer (CRC) is among the most prevalent malignancies globally. Early detection of precancerous lesions through routine colonoscopy has led to a dramatic reduction in CRC-related incidence and mortality among those between the ages of 50 and 70. However, in those where the disease progresses to an advanced stage, chemotherapy remains the primary available treatment option, and the associated 5-year survival rate remains low. The identification of genes associated with CRC chemoresistance would thus be a beneficial approach to identifying novel treatments for this deadly disease.
The expression of circRNA_101277, miR-370, and IL-6 was assessed via qRT-PCR. IL-6 levels were measured with a human IL-6 ELISA kit based on the provided protocols. CRC cellular proliferation and cisplatin IC50 values were quantified via MTT assays. Luciferase assays were used to detect circRNA_101277 and miR-370 binding sites or miR-370 and IL-6 binding sites.
circRNA_101277 was increased in CRC tissues compared with control samples. circRNA_101277 overexpression was evident in CRC cells, and knockdown of this circRNA suppressed cellular proliferation and cisplatin resistance in these cancer cells. At a mechanistic level, circRNA_101277 was found to function by sequestering miR-370, thereby upregulating the miR-370 target gene IL-6 and promoting cisplatin resistance via this miR-370/IL-6 axis.
In summary, our data highlight circRNA_101277 as a novel driver of CRC cell cisplatin resistance that functions by sequestering miR-370 and thereby enhancing IL-6 expression. These findings suggest that this circRNA_101277/miR-370/IL-6 axis may represent a critical axis of chemoresistance in CRC that can be targeted to diagnose and/or treat this cancer.
结直肠癌（CRC）是全球最常见的恶性肿瘤之一。通过常规结肠镜检查早期发现癌前病变，使得 50 至 70 岁人群 CRC 相关发病率和死亡率显著降低。然而，对于疾病进展到晚期的患者，化疗仍然是主要的治疗选择，相关的 5 年生存率仍然较低。因此，鉴定与 CRC 化疗耐药相关的基因将有助于为这种致命疾病找到新的治疗方法。
通过 qRT-PCR 评估 circRNA_101277、miR-370 和 IL-6 的表达。根据提供的方案，使用人 IL-6 ELISA 试剂盒测量 IL-6 水平。通过 MTT 测定法定量测定 CRC 细胞增殖和顺铂 IC50 值。使用荧光素酶测定法检测 circRNA_101277 和 miR-370 结合位点或 miR-370 和 IL-6 结合位点。
与对照样本相比，CRC 组织中 circRNA_101277 增加。在 CRC 细胞中观察到 circRNA_101277 的过表达，并且敲低该 circRNA 可抑制这些癌细胞的细胞增殖和顺铂耐药性。在机制水平上，发现 circRNA_101277 通过与 miR-370 结合而发挥作用，从而上调 miR-370 靶基因 IL-6，并通过该 miR-370/IL-6 轴促进顺铂耐药性。
总之，我们的数据强调 circRNA_101277 是 CRC 细胞顺铂耐药的新型驱动因子，通过与 miR-370 结合并增强 IL-6 表达来发挥作用。这些发现表明，该 circRNA_101277/miR-370/IL-6 轴可能代表 CRC 化疗耐药的关键轴，可用于诊断和/或治疗这种癌症。
