Wang Yiping, Zhang Shuai, Bing Jie, Li Wanjie, Sun Lin, Wang Youjun
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Int J Mol Sci. 2024 Dec 24;26(1):31. doi: 10.3390/ijms26010031.
Cells meticulously regulate free calcium ion (Ca) concentrations, with the endoplasmic reticulum (ER) being crucial for Ca homeostasis. Disruptions in ER Ca balance can contribute to various diseases, including cancer. Although considerable research has focused on the direct mechanisms of ER Ca regulation, the role of microRNAs (miRNAs) in this process remains underexplored. Mainly using data from a CRISPR-based genomic screening previously conducted in our laboratory, we identified 33 candidate miRNAs that may regulate ER Ca levels. From these, 10 miRNAs were found to significantly lower basal ER Ca levels. RNA sequencing analysis indicated that these miRNAs downregulate the tumor suppressor tumor protein p53 (TP53)-inducible protein 11 gene (), which is a key regulator of ER Ca levels. Functional assays confirmed that influences ER Ca levels and affects cancer cell proliferation. Additionally, the chemotherapeutic agent doxorubicin (DOX) was shown to upregulate and enhance ER Ca accumulation. These findings elucidate the central role of TP53I11 in miRNA-mediated regulation of ER Ca homeostasis and suggest potential therapeutic strategies targeting ER Ca upregulation for cancer intervention.
细胞会精确调节游离钙离子（Ca）的浓度，其中内质网（ER）对于钙稳态至关重要。内质网钙平衡的破坏会导致包括癌症在内的各种疾病。尽管大量研究聚焦于内质网钙调节的直接机制，但微小RNA（miRNA）在此过程中的作用仍未得到充分探索。主要利用我们实验室之前进行的基于CRISPR的基因组筛选数据，我们鉴定出33个可能调节内质网钙水平的候选miRNA。其中，发现10个miRNA能显著降低内质网基础钙水平。RNA测序分析表明，这些miRNA下调肿瘤抑制因子肿瘤蛋白p53（TP53）诱导蛋白11基因（），该基因是内质网钙水平的关键调节因子。功能分析证实，影响内质网钙水平并影响癌细胞增殖。此外，化疗药物阿霉素（DOX）被证明可上调并增强内质网钙积累。这些发现阐明了TP53I11在miRNA介导的内质网钙稳态调节中的核心作用，并提出了针对内质网钙上调进行癌症干预的潜在治疗策略。
