Clinical Laboratory Department, Benxi Central Hospital, Benxi 117000, China.
Research Laboratory Department, Benxi Central Hospital, Benxi 117000, China.
Exp Biol Med (Maywood). 2021 Feb;246(4):371-379. doi: 10.1177/1535370220966253. Epub 2020 Nov 11.
Long non-coding RNAs are a kind of endogenous ncRNAs with a length of more than 200 bp. Accumulating evidence suggests that long non-coding RNAs function as pivotal regulators in tumorigenesis and progression. However, their biological roles in breast cancer remain largely unknown. Here, we found that IGF2 antisense RNA (IGF2-AS) was significantly decreased in breast cancer tissues, cell lines, and plasma. Patients with low IGF2-AS were more likely to develop larger tumor size and later clinical stage. Overexpression of IGF2-AS evidently inhibited the proliferation and induced apoptosis of MCF-7 and T47D cells , as well as retarded tumor growth . Further investigation revealed that IGF2-AS inhibited the expression of its sense-cognate gene IGF2 in an epigenetic DNMT1-dependent manner, resulting in the inactivation of downstream oncogenic PI3K/AKT/mTOR signaling pathway. Enforced expression of IGF2 could significantly block the tumor inhibitory effect of IGF2-AS. Importantly, we found that IGF2-AS could be used as an effective biomarker for breast cancer diagnosis and prognosis. Taken together, our study indicates that IGF2-AS is a tumor suppressor in breast cancer, restoration of IGF2-AS may be a promising treatment for this fatal disease.
长非编码 RNA 是一种长度超过 200bp 的内源性 ncRNA。越来越多的证据表明，长非编码 RNA 在肿瘤发生和进展中起着关键的调控作用。然而，它们在乳腺癌中的生物学作用在很大程度上尚不清楚。在这里，我们发现 IGF2 反义 RNA (IGF2-AS) 在乳腺癌组织、细胞系和血浆中显著降低。IGF2-AS 水平低的患者更容易发生更大的肿瘤大小和更晚期的临床分期。IGF2-AS 的过表达明显抑制 MCF-7 和 T47D 细胞的增殖并诱导其凋亡，同时也抑制肿瘤生长。进一步的研究表明，IGF2-AS 通过表观遗传 DNMT1 依赖性方式抑制其同源基因 IGF2 的表达，导致下游致癌 PI3K/AKT/mTOR 信号通路失活。IGF2 的强制表达可显著阻断 IGF2-AS 的肿瘤抑制作用。重要的是，我们发现 IGF2-AS 可作为乳腺癌诊断和预后的有效生物标志物。总之，我们的研究表明 IGF2-AS 是乳腺癌中的肿瘤抑制因子，恢复 IGF2-AS 可能是治疗这种致命疾病的有前途的方法。
