Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, People's Republic of China.
Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 262000, Shandong, People's Republic of China.
Aging (Albany NY). 2021 Apr 20;13(10):13571-13584. doi: 10.18632/aging.202874.
Long intergenic noncoding RNAs (lincRNAs) regulate a series of biological processes, and their anomalous expression plays critical roles in the progression of multiple malignancies, including colorectal cancer (CRC). Although many studies have reported the oncogenic function of LINC00665 in multiple cancers, few studies have explored its role in CRC. The aim of this study was to assess the effect of LINC00665 on the malignant behaviors of CRC and explore the underlying regulatory mechanism of LINC00665. LINC00665 was significantly upregulated in CRC. A loss-of-function assay revealed that LINC00665 downregulation inhibited the proliferation and promoted the apoptosis of CRC cells, which was mediated by cyclin D1, CDK4, caspase-9 and caspase-3. Through mechanistic exploration, we found that miR-126-5p directly bound to LINC00665. Moreover, LINC00665 and miR-126-5p both regulated PAK2 and FZD3 expression. Mechanistically, miR-126-5p was predicted and further verified as a target of both PAK2 and FZD3. These findings demonstrate that LINC00665 might play an important pro-proliferative and antiapoptotic role in CRC and might be a potential biomarker and a new therapeutic target for CRC.
长链非编码 RNA(lncRNA)调节一系列生物学过程,其异常表达在多种恶性肿瘤的进展中起着关键作用,包括结直肠癌(CRC)。尽管许多研究已经报道了 LINC00665 在多种癌症中的致癌功能,但很少有研究探讨其在 CRC 中的作用。本研究旨在评估 LINC00665 对 CRC 恶性行为的影响,并探讨 LINC00665 的潜在调节机制。LINC00665 在 CRC 中显著上调。功能丧失实验表明,LINC00665 下调抑制 CRC 细胞的增殖并促进其凋亡,这是由细胞周期蛋白 D1、CDK4、半胱天冬酶-9 和半胱天冬酶-3介导的。通过机制探索,我们发现 miR-126-5p 可直接与 LINC00665 结合。此外,LINC00665 和 miR-126-5p 均调节 PAK2 和 FZD3 的表达。从机制上讲,miR-126-5p 被预测并进一步验证为 PAK2 和 FZD3 的靶标。这些发现表明,LINC00665 可能在 CRC 中发挥重要的促增殖和抗凋亡作用,可能是 CRC 的潜在生物标志物和新的治疗靶点。