Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan.
Cancer Sci. 2020 Apr;111(4):1076-1083. doi: 10.1111/cas.14357. Epub 2020 Mar 18.
Rat sarcoma (RAS) is a well-known oncogene that plays important roles in cancer proliferation, cell survival and cell invasion. RAS exists as three major isoforms, Kirsten rat sarcoma (KRAS), Harvey rat sarcoma (HRAS) and neuroblastoma rat sarcoma (NRAS). Mutations of these genes account for approximately 30% of all cancers. Among them, KRAS mutations are the most common, responsible for 85%, followed by NRAS (12%) and HRAS (3%). Although the development of RAS inhibitors has been explored for over the past decade, so far, no effective inhibitor has been found. MicroRNA (miRNA) are a class of small non-coding RNA that control the gene expression of pleural target genes at the post-transcriptional level. MiRNA play critical roles in the physiological and pathological processes at work in cancers, such as cell proliferation, cell death, cell invasion and metastasis. MicroRNA-143 (MIR143) is known to function as a tumor suppressor in a variety of cancers. One of its known mechanisms is suppression of RAS expression and its effector signaling pathways, such as PI3K/AKT and MAPK/ERK. Within the last five years, we developed a potent chemically modified MIR143-3p that enabled us to elucidate the details of the KRAS signaling networks at play in colon and other cancer cells. In this review, we will discuss the role of MIR143-3p in those RAS signaling networks that are related to various biological processes of cancer cells. In addition, we will discuss the possibility of the use of MIR143 as a therapeutic drug for targeting RAS signaling networks.
大鼠肉瘤（RAS）是一种众所周知的癌基因，在癌症增殖、细胞存活和细胞侵袭中发挥重要作用。RAS 存在三种主要的同工型，即 Kirsten 大鼠肉瘤（KRAS）、Harvey 大鼠肉瘤（HRAS）和神经母细胞瘤大鼠肉瘤（NRAS）。这些基因的突变约占所有癌症的 30%。其中，KRAS 突变最为常见，占 85%，其次是 NRAS（12%）和 HRAS（3%）。尽管过去十年来一直在探索 RAS 抑制剂的开发，但迄今为止尚未发现有效的抑制剂。microRNA（miRNA）是一类小的非编码 RNA，可在转录后水平控制多个靶基因的表达。miRNA 在癌症中的细胞增殖、细胞死亡、细胞侵袭和转移等生理和病理过程中发挥着关键作用。miR-143（MIR143）被认为在多种癌症中作为肿瘤抑制因子发挥作用。其已知机制之一是抑制 RAS 表达及其效应信号通路，如 PI3K/AKT 和 MAPK/ERK。在过去五年中，我们开发了一种有效的化学修饰的 MIR143-3p，使我们能够阐明在结肠和其他癌细胞中发挥作用的 KRAS 信号网络的细节。在这篇综述中，我们将讨论 MIR143-3p 在与癌细胞各种生物学过程相关的 RAS 信号网络中的作用。此外，我们还将讨论将 MIR143 用作针对 RAS 信号网络的治疗药物的可能性。
