Hedgehog (Hh) signaling primarily functions in the control of mammalian embryonic development but also has roles in cancer. The Hh activation depends on ciliogenesis, a cellular process that describes outgrowth of the primary cilium from cell membrane. Ciliogenesis initiation requires a set of proteins known as planar cell polarity (PCP) effectors. Inturned (INTU) is a PCP effector that reportedly functions synergistically with Hh signaling in basal cell carcinoma, suggesting that INTU has an oncogenic role. In this study, we carried out a pan-cancer investigation on the prognostic significance of INTU in different types of cancer. We demonstrated that INTU downregulation correlated with reduced survival probabilities in lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma (UCEC) patients. Similar expression patterns and prognostic values were identified for intraflagellar transport 88 (IFT88), another Hh pathway-associated gene. We elucidated multiple mechanisms at transcriptional, post-transcriptional and translational levels that involved transcription factor 4 and non-coding RNAs-associated regulatory networks contributing to the reduction of INTU and IFT88 levels in LUAD and UCEC samples. Taken together, this study demonstrates the prognostic significance of the Hh-related genes INTU and IFT88 in LUAD and UCEC and further delineates multifaceted mechanisms leading to INTU and IFT88 downregulation in tumor samples.

中文翻译：

---

多方面的研究揭示了肺腺癌和子宫体子宫内膜癌中 Hedgehog 通路相关基因 INTU 和 IFT88 下调的多种机制


Hedgehog (Hh) 信号主要在控制哺乳动物胚胎发育中发挥作用，但也在癌症中发挥作用。 Hh 激活取决于纤毛发生，这是一种描述初级纤毛从细胞膜生长出来的细胞过程。纤毛发生的启动需要一组称为平面细胞极性（PCP）效应器的蛋白质。 Inturned (INTU) 是一种 PCP 效应子，据报道在基底细胞癌中与 Hh 信号传导具有协同作用，表明 INTU 具有致癌作用。在本研究中，我们对INTU在不同类型癌症中的预后意义进行了泛癌研究。我们证明INTU下调与肺腺癌 (LUAD) 和子宫体子宫内膜癌 (UCEC) 患者的生存概率降低相关。另一种 Hh 通路相关基因鞭毛内转运 88 ( IFT88 ) 也具有相似的表达模式和预后价值。我们阐明了转录、转录后和翻译水平的多种机制，涉及转录因子 4 和非编码 RNA 相关调控网络，有助于降低 LUAD 和 UCEC 样本中INTU和IFT88水平。综上所述，本研究证明了 Hh 相关基因INTU和IFT88在 LUAD 和 UCEC 中的预后意义，并进一步阐明了导致肿瘤样本中INTU和IFT88下调的多方面机制。