Identification of TMEM115 as a tumor suppressor gene through TERT regulation in pancreatic cancer

The catalytic component of telomerase, telomerase reverse transcriptase (TERT), is reactivated in immortalized cells and plays a crucial role in cancer development. Pancreatic cancer (PC) is frequently associated with loss of heterozygosity on the short arm of human chromosome 3. In a previous study, chromosome engineering experiments in PC suggested that putative TERT suppressor genes (TSGs) are present on the 3p21.3 region. Here, we performed functional analysis using a human artificial chromosome (HAC) carrying only the 3p21.3 region (3p21.3-HAC) to directly clarify if TSGs are contained in the 3p21.3 region. We observed reduced TERT transcription following the introduction of 3p21.3-HAC into PC cells. Furthermore, to identify the specific TSGs in the 3p21.3 region, we performed RNA sequencing analysis using mouse Tert (mTert)-expressing murine LTPA PC cells containing either 3p21.3-HAC or the empty HAC vector. Through this analysis, we identified transmembrane protein 115 (TMEM115) as a novel TSG. Furthermore, both human TERT (hTERT) and mTert transcription can be suppressed by TMEM115. Thus, TMEM115 may contribute to PC development by functioning as a novel telomerase regulating factor via controlling TERT expression.