Dari Mahrokh Abouali Gale, Radmehr Safa, Khodadadi Ali, Shooshtari Maryam Khombi, Kempisty Bartosz, Farzaneh Maryam, Sheykhi-Sabzehpoush Mohadeseh
Department of Obstetrics and Gynecology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Curr Mol Med. 2025 Jan 6. doi: 10.2174/0115665240336515241124151446.
Long non-coding RNAs (lncRNAs) play vital roles in the development and progression of various tumors through multiple mechanisms. Among these, HOTTIP (HOXA transcript at the distal tip) stands out as an intriguing candidate with diverse functions in several malignancies, including breast cancer and gynecologic cancers such as ovarian, cervical, and endometrial cancers, which are significant global health concerns. HOTTIP interacts with key signaling pathways associated with these cancers, including Wnt/β-catenin, PI3K/AKT, and MEK/ERK pathways, enhancing their activation and downstream effects. Its influence extends to crucial aspects of cancer biology, such as cell proliferation, apoptosis, migration, invasion, angiogenesis, and epithelial-mesenchymal transition (EMT). Additionally, HOTTIP plays a pivotal role in the pathogenesis of breast and gynecologic tumors by sponging various microRNAs (miRNAs) and regulating the expression of mRNAs involved in critical molecular processes. This dysregulation is often associated with poor clinical outcomes, advanced disease stages, and distant metastases. Understanding the functional roles of HOTTIP in these cancers is essential for developing targeted therapeutic strategies. This review aims to explore the emerging roles of HOTTIP in breast and gynecologic cancers.
长链非编码RNA（lncRNAs）通过多种机制在各种肿瘤的发生发展过程中发挥着至关重要的作用。其中，HOTTIP（HOXA基因远端转录本）作为一个引人关注的候选分子脱颖而出，它在包括乳腺癌以及卵巢癌、宫颈癌和子宫内膜癌等妇科癌症在内的多种恶性肿瘤中具有多种功能，而这些癌症都是全球重大的健康问题。HOTTIP与这些癌症相关的关键信号通路相互作用，包括Wnt/β-连环蛋白、PI3K/AKT和MEK/ERK通路，增强它们的激活及下游效应。其影响延伸至癌症生物学的关键方面，如细胞增殖、凋亡、迁移、侵袭、血管生成以及上皮-间质转化（EMT）。此外，HOTTIP通过吸附各种微小RNA（miRNAs）并调节参与关键分子过程的mRNA的表达，在乳腺和妇科肿瘤的发病机制中发挥关键作用。这种失调通常与不良临床结果、疾病晚期以及远处转移相关。了解HOTTIP在这些癌症中的功能作用对于制定靶向治疗策略至关重要。本综述旨在探讨HOTTIP在乳腺癌和妇科癌症中新兴的作用。
