Long noncoding RNA TMEM75 promotes colorectal cancer progression by activation of SIM2

Colorectal cancer (CRC) is one of the most frequent cancers worldwide and leads to a great many deaths each year. However, the underlying mechanisms that regulate colorectal cancer development and progression remain elusive. Here we identified an uncharacteristic long noncoding RNA TMEM75 that was upregulated in colorectal cancer compared to non-tumor tissues. We found that TMEM75 expression levels are positively correlated with advanced clinical stage. TMEM75 significantly inhibited the proliferation, migration, and invasion of CaCo2 and HCT116 cells in vitro. Moreover, TMEM75 silence delayed tumor growth in vivo. Mechanistically, TMEM75 was demonstrated to initiate the expression of transcription factor SIM2. We also found that the expression of SIM2 was upregulated and positively correlated that of TMEM75 in colorectal cancer tissues. Furthermore, ectopic expression of SIM2 rescued TMEM75 depletion-induced inhibition on cell proliferation, migration and invasion in colorectal cancer. Altogether, our findings indicated that TMEM75 functions as an oncogene relying on activation of SIM2 in colorectal cancer for the first time.