Yadollahi-Farsani Mahtab, Amini-Farsani Zeinab, Moayedi Fatemeh, Khazaei Niusha, Yaghoobi Hajar
Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
IUBMB Life. 2023 Feb;75(2):97-116. doi: 10.1002/iub.2688. Epub 2022 Dec 24.
Breast cancer is the most aggressive and fatal form of cancer among women globally. Although the role of some miRNAs that are often dysregulated in breast cancer has been deciphered, the regulatory function of others still remains unknown. The current study was aimed at determining the biological role and underlying mechanism of miR-548k in breast cancer. In this study, the significant overexpression of miR-548k in breast cancer tissues compared to adjacent normal tissues was confirmed. Also, bioinformatics analysis indicated that PTEN, as a negative regulator of PI3K/AKT signaling pathway, was a potential target of miR-548k, and its expression was downregulated in breast cancer tissues rather than normal tissues. Furthermore, the ectopic increase of miR-548k decreased the expression of PTEN in breast cancer, suggesting that PTEN is one of the potential downstream targets of miR-548k. Besides, functional analysis was conducted to assess the capability of miR-548k to alter apoptosis along with the changed expression levels of miR-548k in breast cancer cells. Based on this investigation, forced increase of miR-548k disrupted programmed cell death in MCF-7 cells. Apart from this, in silico study of miR-548 family supported its association with the main components of PI3K/Akt signaling pathway, opening a prospective research area in cancer therapy. In brief, suppression of PTEN partly mediated by miR-548k diminished apoptosis and promoted cell proliferation through PI3K/Akt pathway in breast cancer, suggesting a novel therapeutic axis, miR-548k/PTEN/ PI3K/Akt, for treatment of breast cancer in the future.
乳腺癌是全球女性中最具侵袭性和致命性的癌症形式。尽管一些在乳腺癌中经常失调的微小RNA（miRNA）的作用已被破解，但其他一些miRNA的调节功能仍不清楚。本研究旨在确定miR-548k在乳腺癌中的生物学作用及潜在机制。在本研究中，证实了与相邻正常组织相比，miR-548k在乳腺癌组织中显著过表达。此外，生物信息学分析表明，作为PI3K/AKT信号通路负调节因子的PTEN是miR-548k的潜在靶标，其在乳腺癌组织中的表达下调，而非正常组织。此外，miR-548k的异位增加降低了乳腺癌中PTEN的表达，表明PTEN是miR-548k潜在的下游靶标之一。此外，进行了功能分析，以评估miR-548k改变凋亡的能力以及其在乳腺癌细胞中表达水平的变化。基于这项研究，miR-548k的强制增加破坏了MCF-7细胞中的程序性细胞死亡。除此之外，对miR-548家族的计算机模拟研究支持了其与PI3K/Akt信号通路主要成分的关联，为癌症治疗开辟了一个前瞻性研究领域。简而言之，miR-548k部分介导的PTEN抑制通过PI3K/Akt途径减少了乳腺癌中的凋亡并促进了细胞增殖，提示了一条新的治疗轴，即miR-548k/PTEN/PI3K/Akt，有望用于未来乳腺癌的治疗。
