Alam Shahil, Giri Pankaj Kumar
Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, India.
Front Oncol. 2024 Mar 13;14:1366223. doi: 10.3389/fonc.2024.1366223. eCollection 2024.
Ovarian Cancer (OC) ranks as a prominent contributor to mortality among female reproductive system associated cancers, particularly the prevalent subtype epithelial Ovarian Cancer (EOC). Despite advancements in treatment modalities, the prognosis for OC patients remains grim due to limitation of current therapeutic methodology such as high cytotoxicity of chemotherapeutic agents and tumor relapse making existing chemotherapy ineffective. Recognizing the limitations of a broad-spectrum approach to treating OC, a shift toward targeted therapies aligning with unique molecular features is imperative. This shift stems from an incomplete understanding of OC's origin, distinguishing it from extensively researched malignancies such as cervical or colon cancer. At the molecular level, postsynthetic modifications-DNA, RNA, and protein-shape transcriptional, posttranscriptional, and posttranslational processes. Posttranscriptional regulatory mechanisms, including RNA modifications are termed epitranscriptomic and play critical roles in this process. For more than five decades, 100+ RNA post-synthetic modifications, notably N6-methyladenosine (m6A), most prevalent RNA modification in mammals, dynamically regulate messenger RNA (mRNA), and non-coding RNA (ncRNA) life orchestrated via writers, erasers, and readers. The disruption of m6A modifications are found in several cancers, including OC, underscores pivotal role of m6A. This review focused on m6A modifications in coding and non-coding RNAs, emphasizing their role as prognostic markers in OC and their impact on development, migration, invasion, and drug resistance. Additionally, RNA-modified regulators have been explored as potential molecular and therapeutic targets, offering an innovative approach to combatting this challenging malignancy.
卵巢癌（OC）是女性生殖系统相关癌症中导致死亡的主要原因，尤其是常见的上皮性卵巢癌（EOC）亚型。尽管治疗方式有所进步，但由于当前治疗方法的局限性，如化疗药物的高细胞毒性和肿瘤复发导致现有化疗无效，OC患者的预后仍然严峻。认识到广谱治疗OC方法的局限性，转向与独特分子特征相匹配的靶向治疗势在必行。这种转变源于对OC起源的不完全理解，这使其有别于宫颈癌或结肠癌等经过广泛研究的恶性肿瘤。在分子水平上，合成后修饰——DNA、RNA和蛋白质——塑造转录、转录后和翻译后过程。包括RNA修饰在内的转录后调控机制被称为表观转录组学，在这一过程中发挥着关键作用。五十多年来，100多种RNA合成后修饰，特别是N6-甲基腺苷（m6A），这是哺乳动物中最普遍的RNA修饰，通过写入器、擦除器和读取器动态调节信使RNA（mRNA）和非编码RNA（ncRNA）的生命历程。在包括OC在内的几种癌症中发现了m6A修饰的破坏，这凸显了m6A的关键作用。本综述重点关注编码RNA和非编码RNA中的m6A修饰，强调它们作为OC预后标志物的作用及其对发育、迁移、侵袭和耐药性的影响。此外，RNA修饰调节剂已被探索为潜在的分子和治疗靶点，为对抗这种具有挑战性的恶性肿瘤提供了一种创新方法。
