<br>LncRNA LIMp27 通过 p27 调节 p53 缺陷癌细胞中的 DNA 损伤反应,Advanced Science

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LncRNA LIMp27 通过 p27 调节 p53 缺陷癌细胞中的 DNA 损伤反应
Advanced Science ( IF 14.3 ) Pub Date : 2023-01-13 , DOI: 10.1002/advs.202204599
Ting La _{1,

2,

3,

4} , Song Chen _{1,

5} , Xiao Hong Zhao _{2,

3} , Shuai Zhou ₁ , Ran Xu _{2,

3} , Liu Teng ₁ , Yuan Yuan Zhang _{2,

3} , Kaihong Ye ₁ , Liang Xu _{2,

3} , Tao Guo ₆ , Muhammad Fairuz Jamaluddin ₃ , Yu Chen Feng _{2,

7} , Hai Jie Tang _{2,

3} , Yanliang Wang ₈ , Qin Xu ₈ , Yue Gu ₈ , Huixia Cao ₈ , Tao Liu ₉ , Rick F Thorne _{1,

3} , Feng-Min Shao ₈ , Xu Dong Zhang _{1,

2,

3} , Lei Jin _{1,

2,

7}

Affiliation

Translational Research Institute, Henan Provincial and Zhengzhou City Key laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People's Hospital, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450053, China.
Noncoding Cancer Biomarkers and Therapeutics Group, Cancer Detection & Therapy Research Program, Hunter Medical Research Institute, Callaghan, New South Wales, 2305, Australia.
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, 2308, Australia.
National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
Institute of Medicinal Biotechnology, Jiangsu College of Nursing, Huai'an, Jiangsu, 223300, China.
Institute of Future Agriculture, Northwest A&F University, Yangling, Shaanxi, 712100, China.
School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, 2308, Australia.
Department of Nephrology, Henan Provincial Key Laboratory of Kidney Disease and Immunology, Henan Provincial Clinical Research Center for Kidney Disease, Henan Provincial People's Hospital, Zhengzhou, Henan, 450053, China.
Children's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, New South Wales, 2750, Australia.

P53 失活发生在大约 50% 的人类癌症中，其中 p53 驱动的 p21 活性缺失，p27 对于 DNA 损伤后 G1/S 检查点的建立至关重要。在这里，这项工作表明 E2F1 反应性 lncRNA LIMp27 选择性抑制 p27 表达，并有助于 p53 缺陷结肠腺癌（COAD）细胞的增殖、致瘤性和治疗耐药性。LIMp27 与 p27 mRNA 竞争结合细胞质定位的 hnRNA0，否则会稳定 p27 mRNA，导致细胞周期停滞在 G0/G1 期。作为对 DNA 损伤的响应，LIMp27 在野生型和 p53 突变型 COAD 细胞中均上调，而细胞质 hnRNPA0 仅在 p53 突变型 COAD 细胞中由于细胞核易位而增加。此外，高 LIMp27 表达与 p53 突变体的不良生存率相关，但与野生型 p53 COAD 患者的生存率低无关。这些结果揭示了促进 p53 缺陷癌症发病机制的 lncRNA 机制，并表明 LIMp27 可能构成治疗此类癌症的靶点。

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更新日期：2023-01-13

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