<p>MicroRNA-940 restricts the expression of metastasis-associated gene MACC1 and enhances the antitumor effect of Anlotinib on colorectal cancer</p>

Abstract

Background: Metastasis-associated with colon cancer-1 (MACC1) is an important regulator that promotes colorectal cancer (CRC) cells’ proliferation and distant metastasis. Therefore, MACC1 is considered as a promising therapeutic target of CRC. This work aimed to identify the microRNA (miR) targeted to MACC1, and to study the potential of using the particular miR in enhancing the antitumor effect of chemotherapy. Materials and methods: miR prediction was performed in the miR database. The effect of miR-940 on MACC1’s expression was examined by Western blot, and the effect of miR-940 on the expression of genes related to the epithelial–mesenchymal transition (EMT) was identified by quantitative real-time polymerase chain reaction experiments. In vivo growth of CRC cells were analyzed in the nude mice subcutaneous tumor model and CRC liver metastasis model. Results: By using the database, miR-940 was identified to target to the 3ʹUTR of MACC1’s mRNA. Experimentally, transfection of miR-940 decreased the expression of MACC1 in CRC cells and inhibited the EMT process of the transfected cells. MiR-940 also enhanced the inhibitory effect of Anlotinib on CRC cells’ in vivo growth and invasion. Correspondingly, ectopic expression of MACC1 mutant, which does not contain miR-940 binding site, blocked the antitumor effect of miR-940 on CRC cells. Conclusion: MiR-940 restricts the proliferation and invasion of CRC cells by targeting to MACC1’s mRNA, and enhances the antitumor effect of Anlotinib on CRC tumors.

Anlotinib as a molecular targeted therapy for tumors (Review)

“…MicroRNAs (miRs) have a dual role in promoting drug sensitivity and inducing drug resistance in cancer treatment (28,29). A study by Wang et al (30) suggested that silencing the expression of the gene metastasis-associated in colon cancer-1 via miR-940 increased the antitumor effect of anlotinib on the proliferation and invasive growth of CRC cells. Ma et al (31) reported that miR-6077 inhibited the expression of glucose transporter 1 and enhanced the anti-tumor effect of anlotinib on patient-derived lung adenocarcinoma cells.…”

Transcriptome profiling analysis reveals that ATP6V0E2 is involved in the lysosomal activation by anlotinib

“…In patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma, anlotinib also shows promising efficacy [8][9][10][11] . In human colorectal cancer, the antitumor effect of anlotinib can be enhanced by MiR-940 targeting MACC1's mRNA 12 . Similar to that of other receptor tyrosine kinase inhibitors, the combined treatment of anlotinib with chemotherapy does not appear to be more beneficial than anlotinib alone 13 .…”

<p>Analysis of Key Genes Regulating the Warburg Effect in Patients with Gastrointestinal Cancers and Selective Inhibition of This Metabolic Pathway in Liver Cancer Cells</p>

“…31 It has also been reported that MACC1 is strongly associated with MET signaling in liver metastases of resected CRC and is involved in EMT in colorectal cancer. 32,33 However, our analysis showed that it was downregulated in liver cancer. Until now, no studies have been conducted to try to understand the differential expression of MACC1 between primary and metastatic liver tumors.…”