Prognostic Analysis of LncRNA MCM3AP-AS1 in Colorectal Cancer and the Mechanism of Its Effect on Tumor Cell Activity

Abstract

To determine the clinical prognostic significance of lncRNA MCM3AP-AS1 in colorectal cancer (CRC) and its preliminary mechanism, 43 CRC patients and 48 healthy individuals were analyzed. Peripheral blood MCM3AP-AS1 was quantified via qRT–PCR in CRC patients at admission and 2 h after surgery and in healthy individuals. Human colon cancer cells (HCT116 and SW480) were transfected with shRNAs targeting upregulation of MCM3AP-AS1 expression (named as sh-MCM3AP-AS1 group) and corresponding negative RNAs (named as sh-MCM3AP-AS1 group). Additionally, the cells were then treated either with 50 mM of the VEGF-specific inhibitor PTK787 (Selleck, USA) (named as inhibition group) or normal saline as a control (named as control group). Before therapy, CRC patients presented a higher MCM3AP-AS1 level than healthy individuals ( $P<0.05$ ), and the sensitivity and specificity of MCM3AP-AS1 in predicting the occurrence of CRC were 65.12% and 83.33%, respectively ( $P<0.001$ ). After therapy, CRC patients presented a decrease in MCM3AP-AS1 levels, and recurrence was higher in patients who died ( $P<0.05$ ). Additionally, the high MCM3AP-AS1 expression group presented a higher mortality than the low MCM3AP-AS1 expression group ( $P<0.05$ ). In an in vitro assay, CRC cells showed a higher MCM3AP-AS1 level than CCD-18Co cells, and the sh-MCM3AP-AS1 group presented decreased cell proliferation and invasiveness, whereas the levels apoptosis-associated proteins were increased ( $P<0.05$ ). Moreover, the VEGF and VEGFR2 mRNA levels were increased in CRC cells, and VEGF/VEGFR2 pathway-associated proteins were inhibited in the sh-MCM3AP-AS1 group ( $P<0.05$ ). Moreover, treatment with PTK787 decreased cell proliferation and invasivness but increased the levels of apoptosis-associated proteins ( $P<0.05$ ).