Shenzhen Traditional Chinese Medicine Oncology Center, Shenzhen, Guangdong, P. R. China.
Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, P. R. China.
PLoS One. 2024 Nov 15;19(11):e0312417. doi: 10.1371/journal.pone.0312417. eCollection 2024.
Colorectal cancer (CRC) is a prevalent form of malignant tumor, and the current clinical treatments are far from satisfactory. Identifying new therapeutic targets is therefore essential for clinical practices. The long intergenic non-protein coding RNA lincROR has been shown to play a significant role in the tumorigenesis of various cancers. However, the molecular mechanism underlying lincROR-mediated CRC tumorigenesis remains unclear. In the present study, we found that knockdown of lincROR significantly inhibited cell viability in vitro, while its overexpression promoted tumor growth in vivo. Mechanistically, lincROR acted as a miRNA sponge for miR-145, thereby elevating the expression of the target genes WNT2B and WNT10A. The overexpression of WNT2B and WNT10A definitely activated the Wnt/β-catenin pathway, thus led to promoting tumorigenesis in CRC. In summary, our findings identified lincROR as a novel activator of the Wnt/β-catenin pathway by serving as a miRNA sponge for miR-145 and facilitating tumorigenesis, which suggests that lincROR may be a potential therapeutic target for CRC patients.
结直肠癌（CRC）是一种常见的恶性肿瘤，目前的临床治疗方法远不能令人满意。因此，寻找新的治疗靶点对于临床实践至关重要。长链非编码 RNA lincROR 已被证明在多种癌症的肿瘤发生中发挥重要作用。然而，lincROR 介导的 CRC 肿瘤发生的分子机制尚不清楚。在本研究中，我们发现 lincROR 的敲低显著抑制了体外细胞活力，而过表达则促进了体内肿瘤生长。机制上，lincROR 作为 miR-145 的 miRNA 海绵，从而上调了靶基因 WNT2B 和 WNT10A 的表达。WNT2B 和 WNT10A 的过表达肯定激活了 Wnt/β-catenin 通路，从而促进了结直肠癌的肿瘤发生。总之，我们的研究结果表明，lincROR 通过作为 miR-145 的 miRNA 海绵并促进肿瘤发生，充当了 Wnt/β-catenin 通路的新型激活物，这表明 lincROR 可能是 CRC 患者的潜在治疗靶点。
