LINC00114 promotes colorectal cancer metastasis by targeting HNRNPA1 to regulate glutamine metabolism reprogramming and angiogenesis
Colorectal cancer (CRC) is a common type of gastrointestinal malignancy, and it has a close connection with long noncoding RNAs (lncRNAs). This study aims to examine the involvement of long noncoding RNA LINC00114, which targets heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) in regulating glutamine metabolism and angiogenesis in the metastasis of colorectal cancer (CRC). LINC00114 and HNRNPA1 levels are measured in CRC tissues and cells to determine their expression levels. Then, siRNA targeting LINC00114 (si-LINC00114) is used to transfect CRC cells, and cell proliferation and metastasis are detected. The influence of exogenous glucose and glutamine supplementation on angiogenesis induced by LINC00114 in CRC is investigated in HUVECs. Glutamine metabolism in CRC cells is also detected. Furthermore, the role of LINC00114 in CRC xenograft tumors is studied in vivo. LINC00114 and HNRNPA1 are highly expressed in CRC and positively correlate with CD31. si-LINC00114 significantly inhibits proliferation, metastasis and HNRNPA1 expression in CRC cells. An RNA-binding-protein immunoprecipitation (RIP) assay confirms that LINC00114 can bind to HNRNPA1 and positively regulate its expression. Further experiments confirm that si-LINC00114 significantly inhibits cell proliferation and tubule formation in HUVECs. Exogenous glucose and glutamine supplementation significantly promotes the levels of LINC00114 and HNRNPA1 in CRC cells and promotes tubule formation in HUVECs. In addition, transfection of CRC cells with si-LINC00114 and/or oe-HNRNPA1 regulates glutamine metabolism in CRC cells. Animal studies confirm that intervention with LINC00114 represses the progression and vascular normalization of CRC and regulates glutamine metabolism. In conclusion, LINC00114 promotes CRC metastasis by targeting HNRNPA1 to regulate glutamine metabolic reprogramming and angiogenesis.