Long non-coding RNA COL4A2-AS1 facilitates cell proliferation and glycolysis of colorectal cancer cells via miR-20b-5p/hypoxia inducible factor 1 alpha subunit axis

Abstract

Long non-coding RNAs (lncRNAs) have critical functions in tumorigenesis and progression of colorectal cancer (CRC). The role of lncRNA COL4A2-AS1 (COL4A2-AS1) lacks system investigation. The current study comprehensively analyzed the expression, biological functions, and mechanism of COL4A2-AS1 in CRC through performing real-time quantitative PCR (RT-qPCR), Western blot, cell transfection, cell colony assay, MTT assay, flow cytometry and dual-luciferase reporter system assays. A xenograft model of CRC was constructed to further verify the function of COL4A2-AS1 in CRC progression in vivo. The data revealed an upregulated expression of COL4A2-AS1 in CRC tissues and cell lines than paired adjacent tissues and normal cell line. Silencing COL4A2-AS1 inhibited proliferation, aerobic glycolysis, and promoted apoptosis of CRC cells in vivo and in vitro. However, overexpression of COL4A2-AS1 significantly promoted CRC cell proliferation and aerobic glycolysis. In CRC cells, miR-20b-5p was sponged by COL4A2-AS1 and hypoxia-inducible factor 1 alpha subunit (HIF1A). Restoration of HIF1A expression reversed the inhibitory effects of silencing COL4A2-AS1 on aerobic glycolysis and proliferation of CRC cells. The current findings showed that COL4A2-AS1 promoted the proliferation, and aerobic glycolysis of CRC cells potentially through modulating the miR-20b-5p/HIF1A axis.

Long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) promotes the inflammation and apoptosis of otitis media with effusion through targeting microRNA (miR)-495 and activation of p38 MAPK signaling pathway

“…Previous studies indicated that miRNAs could inhibit the inflammatory response by inhibiting the activation of p38 MAPK signaling [ 20 ]. Western blot showed that the upregulation of NEAT1 alone increased the expression of phosphorylated p38 MAPK, while NEAT1 overexpression combined with miR-495 mimics significantly decreased their expressions ( Figure 5a ).…”

“…Thereafter, the cell suspension was supplemented with Annexin V-FITC solution (5 μl) and PI solution (5 μl) followed by 15 minutes incubation in darkness. The cell apoptotic rate was analyzed and was detected by FACSCalibur Flow Cytometer (Becton Dickinson) [ 20 ].…”

microRNA-20b-5p overexpression combing Pembrolizumab potentiates cancer cells to radiation therapy via repressing programmed death-ligand 1

“…However, emerging studies have found that tumors gain resistance to Pembrolizumab or the other immune checkpoint inhibitors therapy [ 42 ]. It is recognized that eribulin is a highly effective anti-tumor drug that has been approved for pretreatment of metastatic breast cancer, and a controlled clinical trial demonstrated that Pembrolizumab in combination with eribulin was more effective than eribulin alone in the treatment of metastatic breast cancer [ 43 , 44 ]. Here, Pembrolizumab is identified to enhance the radiosensitivity of tumor cells in vitro and in vivo , facilitating miR-20b-5p and choking the PD-L1/PD1 pathway.…”

Emerging role of non-coding RNAs in glucose metabolic reprogramming and chemoresistance in colorectal cancer

“…The study by Yu Z et al. has reported that miR-20b-5p was bound with lncRNA COL4A2-AS1, which facilitated the glycolysis of CRC cells by activating HIF-1α ( 68 ). Accordingly, HIF-1a-dependent lnRNAs serve as promising approaches for CRC treatment by controlling glucose metabolic balance.…”