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<p>The catalytic component of telomerase, telomerase reverse transcriptase (<i>TERT</i>), 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 tumor suppressor genes (TSGs) that act through <i>TERT</i> regulation are present on the 3p21.3 region. Here, we performed functional analysis using a human artificial chromosome (HAC) carrying only the&#xa0;3p21.3 region (3p21.3-HAC) to directly clarify if TSGs are contained in the 3p21.3 region. We observed reduced <i>TERT</i> transcription following the introduction of 3p21.3-HAC into PC cells. Furthermore, to identify the specific TSGs functioning via <i>TERT</i> regulation in the 3p21.3 region, we performed RNA sequencing analysis using mouse <i>Tert</i> (<i>mTert</i>)-expressing murine LTPA PC cells containing either 3p21.3-HAC or the empty HAC vector. Through this analysis, we identified transmembrane protein 115 (<i>TMEM115</i>) as a novel TSG. Furthermore, both human <i>TERT</i> (<i>hTERT</i>) and <i>mTert</i> transcription can be suppressed by <i>TMEM115</i>. Thus, <i>TMEM115</i> may contribute to PC development by functioning as a novel telomerase regulating factor via influencing <i>TERT</i> expression.</p>

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Identification of TMEM115 as a tumor suppressor gene and clinical prognostic factor that influences TERT expression in pancreatic cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月24日

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  • Yu Sakano,
  • Takahito Ohira,
  • Haruka Ooi,
  • Miyu Murata,
  • Takuki Yagyu,
  • Yuji Nakayama,
  • Tomohiko Sakabe,
  • Teruhisa Sakamoto,
  • Yoshihisa Umekita,
  • Yoshiyuki Fujiwara,
  • Hiroyuki Kugoh

摘要

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 tumor suppressor genes (TSGs) that act through TERT regulation 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 functioning via TERT regulation 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 influencing TERT expression.