Linc00662 Promotes Tumorigenesis and Progression by Regulating miR-497-5p/AVL9 Axis in Colorectal Cancer

Abstract

Background: Recently, multiple lines of evidence have demonstrated that linc00662 serves as an oncogene in various cancers. However, the exact mechanism of oncogenesis mediated by linc00662 in colorectal cancer (CRC) remains unknown. In this study, we aimed to explore the biological role of linc00662 in the regulation of CRC progression.Methods: Both gene expression omnibus (GEO) and the cancer genome atlas (TCGA) datasets were used to evaluate the expression of linc00662. RT-qPCR was used to analyze the expression of linc00662, miR-497-5p, and AVL9 in CRC clinical samples and cell lines. Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assay, and xenograft model were used to investigate the effect of linc00662 on CRC cell proliferation, cell cycle, and metastasis. Western blot analysis was used to analyze the expression of the epithelial-mesenchymal transition (EMT)-associated markers. Furthermore, bioinformatics analysis and mechanism assays were used to elucidate the underlying mechanism. Dual-luciferase reporter assays were used to analyze the regulatory relationships among linc00662, miR-497-5p, and AVL9.Results: In this study, we found that the expression of linc00662 was significantly upregulated in CRC tissues compared to normal tissues and positively correlated with tissue differentiation, T stage, and lymphatic metastasis. Further, our data showed that the expression of linc00662 was positively associated with lymph node metastasis, TMN stage, and poor-moderate differentiation. Patients with higher linc00662 expression level were more likely to have poorer overall survival. Knockdown of linc00662 inhibited CRC cell growth, induced cell apoptosis, triggered cell cycle arrest at G2/M phase, and suppressed cell migration and invasion through regulating the EMT pathway. Further, mechanistic studies revealed that knockdown of linc00662 significantly reduced the expression of AVL9, a direct target of miR-497-5p.Conclusions: Linc00662 was significantly upregulated in CRC, and mediated CRC progression and metastasis by competing with miR-497-5p to modulate the expression of AVL9. Therefore, our result sheds light on the potential application of linc00662 in CRC diagnosis and therapy.

LINC00662 sponges miR-107 accelerating the invasiveness and proliferation of glioma cells

“…Liu et al showed that high LINC00662 expression contributed acute myeloid leukemia cells growth via targeting the miR-340-5p/ROCK1 axis [22]. Wang et al showed that LINC00662/ miR-497-5p/AVL9 axis promoted colorectal cancer tumorigenesis [23]. Consistent with earlier studies, we showed LINC00662 expression is significantly overexpressed in clinically advanced gliomas.…”

<p>LINC00662 Long Non-Coding RNA Knockdown Attenuates the Proliferation, Migration, and Invasion of Osteosarcoma Cells by Regulating the microRNA-15a-5p/Notch2 Axis</p>

“…37 Notably, LINC00662 knockdown suppresses the growth, migration, and invasion of colorectal cancer cells via regulating the miR-497-5p/AVL9 axis. 15 In the present study, LINC00662 knockdown reduced the proliferation, migration, and invasion of OS cells. The function of LINC00662 identified herein was similar to the results of the aforementioned studies, and indicates that LINC00662 could serve as a promising therapeutic target for OS.…”

“…14 LINC00662 accelerates tumorigenesis and the progression of colorectal cancer by modulating the miR-497-5p/AVL9 axis. 15 However, despite numerous studies on LINC00662, the precise role of LINC00662 in the progression of OS remains unclear.…”

LINC00662 promotes cell viability and metastasis in esophageal squamous cell carcinoma by sponging miR‐340‐5p and upregulating HOXB2

“…Upregulation of LINC00662 has been detected in colorectal cancer and chordoma. 8,9 Functionally, LINC00662-miR-15b-5p mediated GPR120 dysregulation contributed to osteoarthritis., 10 and lncRNA LINC00662 was found to promote colon cancer tumor growth and metastasis by competitively binding with miR-340-5p to regulate CLDN8 expression. 11 miR-340 has been reported to inhibit ESCC cell growth and invasion by targeting phosphoserine aminotransferase 1.…”