Long intergenic noncoding RNA 00665 promotes proliferation and inhibits apoptosis in colorectal cancer by regulating miR-126-5p

Abstract

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.

The Emerging Roles of LINC00665 in Human Cancers

“… Wu et al (2021) measured the expression of LINC00665 by qRT-PCR in 67 colorectal cancer tissues and their matched adjacent healthy tissues. They found significant upregulation of LINC00665 in colorectal cancer tissues compared to healthy control tissues.…”

“…They found that the high expression of LINC00665 in tumor tissues was significantly related to regional lymph node metastasis and poor colorectal cancer tissue differentiation in patients. Experiments in vitro revealed that LINC00665 knockdown could inhibit the proliferation, migration, and invasion of colorectal cancer cells and induce apoptosis in colorectal cancer cells ( Zhao et al, 2020c ; Han et al, 2021 ; Wu et al, 2021 ). Mechanistically, researchers used StarBase to predict the targeted miRNA of LINC00665 and found that miR-9-5p was one of the candidate targets of LINC00665 ( Zhao et al, 2020c ).…”

“…They conclude that LINC00665 promoted the progression of colorectal cancer by regulating the miR-9-5p/ATF1 axis ( Zhao et al, 2020c ). Another study found that LINC00665 could upregulate the expression of PAK2 and FZD3 through sponging miR-126-5p ( Wu et al, 2021 ). Han et al (2021) found that LINC00665 could activate the Wnt/β-catenin signaling pathway by upregulating the expression of CTNNB1, ultimately stimulating the tumorigenicity of colorectal cancer.…”

“…Emerging evidence has indicated that lncRNAs play a crucial role in the occurrence and progression of colorectal cancer (Chen and Shen, 2020). Wu et al (2021) measured the expression of LINC00665 by qRT-PCR in 67 colorectal cancer tissues and their matched adjacent healthy tissues. They found significant upregulation of LINC00665 in colorectal cancer tissues compared to healthy control tissues.…”

“…Existing studies have revealed that lncRNAs are involved in a variety of biological processes, including tumor cell proliferation (Wang et al, 2020a), apoptosis (Zhao et al, 2020a), epithelial to mesenchymal transition (EMT) (McCabe and Rasmussen, 2021), migration (Dhamija and Diederichs, 2016), invasion (Dhamija and Diederichs, 2016), drug resistance (Wei et al, 2020), angiogenesis (Zhao et al, 2020b), and metabolism (Lin, 2020). Although many studies have revealed the expression level and function Hepatocellular carcinoma oncogene upregulated proliferation, migration, invasion, apoptosis, autophagy, glycolysis miR-186-5p/MAP4K3; miR-214-3p/ MAPK1, NF-κB/LINC00665/PKR/ NF-κB Wen et al (2018), Shan and Li (2019), Ding et al (2020), Wan et al (2021) Colorectal cancer oncogene upregulated proliferation, migration, invasion, apoptosis, cell cycle miR-9-5p/ATF1; miR-126-5p/PAK2, FZD3, miR-214-3p, U2AF2/ CTNNB1/Wnt/β-catenin (Zhao et al, 2020c;Han et al, 2021;Wu et al, 2021) Ovarian cancer oncogene upregulated proliferation, migration, invasion, autophagy miR-34a-5p/E2F3; miR-146a-5p/ CXCR4 of lncRNAs in human cancers, the detailed regulatory mechanisms of many lncRNAs in the occurrence and progression of human cancers are still unknown. LINC00665 (also called CIP2A-BP) is a novel lncRNA located on chromosome 19q13.12 and abnormally expressed in many cancers (Figure 1).…”