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miR-326 过表达通过靶向 PNO1 抑制结直肠癌细胞生长和蛋白酶体活性：揭示一种新的治疗干预策略。

miR-326 overexpression inhibits colorectal cancer cell growth and proteasome activity by targeting PNO1: unveiling a novel therapeutic intervention strategy.

机构信息

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.

Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.

出版信息

Sci Rep. 2024 Oct 16;14(1):24284. doi: 10.1038/s41598-024-75746-x.

DOI:10.1038/s41598-024-75746-x
PMID:39414903
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11484865/
Abstract

Proteasome inhibition emerges as a promising strategy for cancer prevention. PNO1, pivotal for colorectal cancer (CRC) progression, is involved in proteasome assembly in Saccharomyces cerevisiae. Hence, we aimed to explore the role of PNO1 in proteasome assembly and its up- and down-streams in CRC. Here, we demonstrated that PNO1 knockdown suppressed CRC cells growth, proteasome activities and assembly, as well as CDKN1B/p27Kip1 (p27) degradation. Moreover, p27 knockdown partially attenuated the inhibition of HCT116 cells growth by PNO1 knockdown. The up-stream studies of PNO1 identified miR-326 as a candidate miRNA directly targeting to CDS-region of PNO1 and its overexpression significantly down-regulated PNO1 protein expression, resulting in suppression of cell growth, decrease of proteasome activities and assembly, as well as increasing the stability of p27 in CRC cells. These findings indicated that miR-326 overexpression can suppress CRC cell growth, acting as an endogenous proteasome inhibitor by targeting PNO1.

摘要

蛋白酶体抑制作用成为癌症预防的一种有前途的策略。PNO1 是结直肠癌（CRC）进展的关键，它参与酿酒酵母中蛋白酶体的组装。因此，我们旨在探索 PNO1 在 CRC 中的蛋白酶体组装及其上下游作用。在这里，我们证明了 PNO1 敲低抑制了 CRC 细胞的生长、蛋白酶体的活性和组装，以及 CDKN1B/p27Kip1（p27）的降解。此外，p27 敲低部分减弱了 PNO1 敲低对 HCT116 细胞生长的抑制作用。对 PNO1 的上游研究确定了 miR-326 是一种候选 miRNA，它可以直接靶向 PNO1 的 CDS 区域，其过表达显著下调 PNO1 蛋白表达，从而抑制细胞生长、降低蛋白酶体活性和组装，以及增加 CRC 细胞中 p27 的稳定性。这些发现表明，miR-326 的过表达可以通过靶向 PNO1 抑制 CRC 细胞的生长，作为内源性蛋白酶体抑制剂发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/cb1639c9bc8a/41598_2024_75746_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/573c08836a5c/41598_2024_75746_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/323ac8e8332b/41598_2024_75746_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/0942ad51bd6d/41598_2024_75746_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/f329db2aa7aa/41598_2024_75746_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/cb1639c9bc8a/41598_2024_75746_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/573c08836a5c/41598_2024_75746_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/e8f7bc0cd744/41598_2024_75746_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/a8ef95854825/41598_2024_75746_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/323ac8e8332b/41598_2024_75746_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/0942ad51bd6d/41598_2024_75746_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/f329db2aa7aa/41598_2024_75746_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a0/11484865/cb1639c9bc8a/41598_2024_75746_Fig7_HTML.jpg

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