The interplay of p16INK4a and non-coding RNAs: bridging cellular senescence, aging, and cancer.

IF 4.4 4区医学 Q1 GERIATRICS & GERONTOLOGY Biogerontology Pub Date : 2025-02-05 DOI:10.1007/s10522-025-10194-2

Ashok Kumar Balaraman, Muhammad Afzal, Ehssan Moglad, M Arockia Babu, G Padma Priya, Pooja Bansal, Sumit Rajotiya, Benod Kumar Kondapavuluri, Imran Kazmi, Sami I Alzarea, Kavita Goyal, Haider Ali

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Abstract

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.

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p16INK4a 是一种重要的肿瘤抑制因子和细胞衰老调节因子，是衰老与癌症之间的分子桥梁。p16INK4a 的表达失调与早衰和癌症进展都有关联，其中非编码 RNA（ncRNA），如长非编码 RNA（lncRNA）、microRNA（miRNA）和小干扰 RNA（siRNA）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通路。在这篇综述中，我们将探讨包括 ANRIL、MIR31HG、UCA1、MALAT1、miR-24、miR-30 和 miR-141 在内的 ncRNA，它们共同调控 p16INK4a 的表达，促进或抑制与癌症和衰老相关的通路。ANRIL 和 MIR31HG 通过与多聚核抑制复合体（PRC）相互作用来调节 p16INK4a 的沉默，而 miR-24 和 miR-30 等 miRNA 则以 p16INK4a 为靶标，影响细胞的增殖和衰老。这种调控相互作用凸显了 ncRNA 靶向策略恢复 p16INK4a 功能的治疗潜力。我们总结了最近的一些研究，这些研究支持控制 p16INK4a 的 ncRNA 可作为诊断生物标志物以及老年相关疾病和癌症的治疗靶点。

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来源期刊

Biogerontology 医学-老年医学

CiteScore

8.00

自引率

4.40%

发文量

审稿时长

>12 weeks

期刊介绍： The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.