a Thoracic surgery ward one , HeNan Provincial Chest Hospital , Zhengzhou , P.R. China.
Cancer Biol Ther. 2019;20(8):1127-1135. doi: 10.1080/15384047.2019.1598762. Epub 2019 Apr 12.
Circular RNA (circRNA) is a new class of non-coding RNA that plays a pivotal role in carcinogenesis. Recently, circ-MTO1 (hsa_circ_0007874) was shown to be a cancer-related circRNA. However, its role in lung adenocarcinoma (LUAD) has not been reported. Here, we found that circ-MTO1 was significantly down-regulated in LUAD, which was closely associated with malignant features and dismal prognosis. Enforced expression of circ-MTO1 suppressed the growth of LUAD cells both and . Subsequent mechanism experiments showed that circ-MTO1 served as a sponge of oncogenic miR-17 to increase the expression of RNA-binding protein QKI-5, leading to the inactivation of Notch signaling pathway, thereby restraining the growth of LUAD. Importantly, increased QKI-5 expression caused by circ-MTO1 overexpression in turn promoted circ-MTO1 expression. Clinically, circ-MTO1 expression was strongly positively correlated with QKI-5 expression, but negatively correlated with miR-17 expression. Taken together, our data suggest that circ-MTO1 is a critical negative regulator of LUAD and elucidate the potential molecular mechanism of a novel circ-MTO1/miR-17/QKI-5 feedback loop in inhibiting LUAD progression.
环状 RNA（circRNA）是一类新的非编码 RNA，在致癌作用中发挥关键作用。最近，circ-MTO1（hsa_circ_0007874）被证明是一种与癌症相关的 circRNA。然而，其在肺腺癌（LUAD）中的作用尚未报道。在这里，我们发现 circ-MTO1 在 LUAD 中显著下调，与恶性特征和预后不良密切相关。circ-MTO1 的过表达抑制了 LUAD 细胞的生长，无论是在体外还是体内。后续的机制实验表明，circ-MTO1 作为致癌 miR-17 的海绵，增加 RNA 结合蛋白 QKI-5 的表达，导致 Notch 信号通路失活，从而抑制 LUAD 的生长。重要的是，circ-MTO1 过表达引起的 QKI-5 表达增加反过来又促进了 circ-MTO1 的表达。临床上，circ-MTO1 的表达与 QKI-5 的表达呈强烈正相关，而与 miR-17 的表达呈负相关。总之，我们的数据表明 circ-MTO1 是 LUAD 的关键负调控因子，并阐明了 circ-MTO1/miR-17/QKI-5 反馈环在抑制 LUAD 进展中的潜在分子机制。
