Balaraman Ashok Kumar, Afzal Muhammad, Moglad Ehssan, Babu M Arockia, Priya G Padma, Bansal Pooja, Rajotiya Sumit, Kondapavuluri Benod Kumar, Kazmi Imran, Alzarea Sami I, Goyal Kavita, Ali Haider
Research and Enterprise, University of Cyberjaya, Persiaran Bestari, Cyber 11, 63000, Cyberjaya, Selangor, Malaysia.
Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, 21442, Jeddah, Saudi Arabia.
Biogerontology. 2025 Feb 5;26(2):50. doi: 10.1007/s10522-025-10194-2.
p16INK4a is a crucial tumor suppressor and regulator of cellular senescence, forming a molecular bridge between aging and cancer. Dysregulated p16INK4a expression is linked to both premature aging and cancer progression, where non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs) play key roles in modulating its function. These ncRNAs interact with p16INK4a through complex post-transcriptional and epigenetic mechanisms, influencing pathways critical to senescence and tumor suppression. In this review, we explore ncRNAs, including ANRIL, MIR31HG, UCA1, MALAT1, miR-24, miR-30, and miR-141, which collectively regulate p16INK4a expression, promoting or inhibiting pathways associated with cancer and aging. ANRIL and MIR31HG modulate p16INK4a silencing via interactions with polycomb repressive complexes (PRC), while miRNAs such as miR-24 and miR-30 target p16INK4a to influence cellular proliferation and senescence. This regulatory interplay underscores the therapeutic potential of ncRNA-targeted strategies to restore p16INK4a function. We summarize recent studies supporting that ncRNAs that control p16INK4a may be diagnostic biomarkers and therapeutic targets for age-related diseases and cancer.
p16INK4a是一种关键的肿瘤抑制因子和细胞衰老调节因子，在衰老与癌症之间形成了一座分子桥梁。p16INK4a表达失调与早衰和癌症进展均有关联，其中长链非编码RNA（lncRNA）、微小RNA（miRNA）和小干扰RNA（siRNA）等非编码RNA（ncRNA）在调节其功能方面发挥着关键作用。这些ncRNA通过复杂的转录后和表观遗传机制与p16INK4a相互作用，影响对衰老和肿瘤抑制至关重要的信号通路。在本综述中，我们探讨了包括ANRIL、MIR31HG、UCA1、MALAT1、miR - 24、miR - 30和miR - 141在内的ncRNA，它们共同调节p16INK4a的表达，促进或抑制与癌症和衰老相关的信号通路。ANRIL和MIR31HG通过与多梳抑制复合物（PRC）相互作用调节p16INK4a的沉默，而miR - 24和miR - 30等miRNA靶向p16INK4a以影响细胞增殖和衰老。这种调节相互作用突出了针对ncRNA的策略在恢复p16INK4a功能方面的治疗潜力。我们总结了最近的研究，支持控制p16INK4a的ncRNA可能是与年龄相关疾病和癌症的诊断生物标志物和治疗靶点。
