MALAT1 promotes colorectal cancer cell proliferation/migration/invasion via PRKA kinase anchor protein 9

• MALAT1 is up-regulated in human primary CRC tissues with lymph node metastasis.
• MALAT1 can be induced via RNA activation.
• MALAT1 plays a critical role in CRC tumor growth and metastasis in mice.
• AKAP-9 is correlated with MALAT1 in CRC tissues.
• AKAP-9 mediates MALAT1 function in CRC proliferation/migration/invasion.

Our previous studies have shown that the 3′ end of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is involved in colorectal cancer (CRC) cell proliferation and migration/invasion in vitro. The role and mechanism of MALAT1 in CRC metastasis in vivo, however, remain largely unknown. In the present study, we found that MALAT1 was up-regulated in human primary CRC tissues with lymph node metastasis. Overexpression of MALAT1 via RNA activation promoted CRC cell proliferation, invasion and migration in vitro, and stimulated tumor growth and metastasis in mice in vivo. Conversely, knockdown of MALAT1 inhibited CRC tumor growth and metastasis. MALAT1 regulated at least 243 genes in CRC cells in a genome-wide expression profiling. Among these genes, PRKA kinase anchor protein 9 (AKAP-9) was significantly up-regulated at both mRNA and protein levels. AKAP-9 was highly expressed in CRC cells with metastatic potential and human primary CRC tissues with lymph node metastasis, but not in normal cells or tissues. Importantly, knockdown of AKAP-9 blocked MALAT1-mediated CRC cell proliferation, migration and invasion. These data indicate that MALAT1 may promote CRC tumor development via its target protein AKAP-9.