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RNF135 通过上调 PI3K/AKT 通路促进人骨肉瘤细胞的生长并抑制细胞凋亡。

RNF135 Promotes Human Osteosarcoma Cell Growth and Inhibits Apoptosis by Upregulating the PI3K/AKT Pathway.

机构信息

Second Department of Orthopedics, Beijing Daxing District People's Hospital, Beijing, China.

Department of Orthopedics, Aerospace Central Hospital, Beijing, China.

出版信息

Cancer Rep (Hoboken). 2024 Aug;7(8):e2159. doi: 10.1002/cnr2.2159.


DOI:10.1002/cnr2.2159
PMID:39118262
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11310095/
Abstract

BACKGROUND: Ring finger protein 135 (RNF135) is an E3 ubiquitin ligase that has been implicated in the tumorigenesis of multiple human malignancies. However, whether RNF135 plays a role in the development of human osteosarcoma (OS) remains unknown. METHODS: RNF135 expression in 20 human OS and 20 human osteochondroma specimens were evaluated by means of immunohistochemistry staining. The effects of shRNA-mediated RNF135 knockdown on human OS cell growth and apoptosis were evaluated through a panel of in vitro studies on cell proliferation, colony formation, exposure of phosphatidylserine on the cell surface, and caspase 3/7 activation. The protein levels of PI3K, AKT, and p-AKT were determined by western blot analysis. RESULTS: We detected significantly higher RNF135 levels in human OS tissues than human osteochondroma tissues. In in vitro studies, shRNA-mediated RNF135 knockdown in human OS cells inhibited proliferation and induced apoptosis. In addition, RNF135 knockdown reduced PI3K and p-AKT protein levels and activated caspase 3 and 7. CONCLUSIONS: These results supported that RNF135 contributes to human OS development through PI3K/AKT-dependent mechanisms. Targeting RNF135 may provide a new therapeutic approach for treating this human malignancy.

摘要

背景:环指蛋白 135(RNF135)是一种 E3 泛素连接酶,与多种人类恶性肿瘤的发生有关。然而,RNF135 是否在人类骨肉瘤(OS)的发展中起作用尚不清楚。

方法:通过免疫组织化学染色评估 20 个人类 OS 和 20 个人类骨软骨瘤标本中的 RNF135 表达。通过体外细胞增殖、集落形成、细胞膜上磷脂酰丝氨酸暴露和 caspase 3/7 激活研究,评估 shRNA 介导的 RNF135 敲低对人骨肉瘤细胞生长和凋亡的影响。通过 Western blot 分析测定 PI3K、AKT 和 p-AKT 的蛋白水平。

结果:我们在人骨肉瘤组织中检测到明显高于人骨软骨瘤组织的 RNF135 水平。在体外研究中,shRNA 介导的人骨肉瘤细胞中 RNF135 敲低抑制增殖并诱导细胞凋亡。此外,RNF135 敲低降低了 PI3K 和 p-AKT 蛋白水平,并激活了 caspase 3 和 7。

结论:这些结果表明,RNF135 通过 PI3K/AKT 依赖性机制促进人类 OS 的发展。针对 RNF135 可能为治疗这种人类恶性肿瘤提供一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb8/11310095/bbc54dccca1d/CNR2-7-e2159-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb8/11310095/09b3b4bea68b/CNR2-7-e2159-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb8/11310095/70df823d3d33/CNR2-7-e2159-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb8/11310095/b8b5fa3ddcb1/CNR2-7-e2159-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb8/11310095/bbc54dccca1d/CNR2-7-e2159-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb8/11310095/09b3b4bea68b/CNR2-7-e2159-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb8/11310095/70df823d3d33/CNR2-7-e2159-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb8/11310095/b8b5fa3ddcb1/CNR2-7-e2159-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb8/11310095/bbc54dccca1d/CNR2-7-e2159-g004.jpg

相似文献

[1]
RNF135 Promotes Human Osteosarcoma Cell Growth and Inhibits Apoptosis by Upregulating the PI3K/AKT Pathway.

Cancer Rep (Hoboken). 2024-8

[2]
Knockdown of Ski decreases osteosarcoma cell proliferation and migration by suppressing the PI3K/Akt signaling pathway.

Int J Oncol. 2019-11-14

[3]
Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway.

Cell Physiol Biochem. 2018

[4]
LncRNA FER1L4 induces apoptosis and suppresses EMT and the activation of PI3K/AKT pathway in osteosarcoma cells via inhibiting miR-18a-5p to promote SOCS5.

Gene. 2019-8-29

[5]
LncRNA LINC00628 overexpression inhibits the growth and invasion through regulating PI3K/Akt signaling pathway in osteosarcoma.

Eur Rev Med Pharmacol Sci. 2018-9

[6]
Knockdown of TBRG4 suppresses proliferation, invasion and promotes apoptosis of osteosarcoma cells by downregulating TGF-β1 expression and PI3K/AKT signaling pathway.

Arch Biochem Biophys. 2020-3-30

[7]
Aplasia Ras homologue member Ⅰ overexpression inhibits tumor growth and induces apoptosis through inhibition of PI3K/Akt survival pathways in human osteosarcoma MG-63 cells in culture.

Int J Mol Med. 2015-9

[8]
Honokiol suppresses proliferation and induces apoptosis via regulation of the miR‑21/PTEN/PI3K/AKT signaling pathway in human osteosarcoma cells.

Int J Mol Med. 2018-1-29

[9]
SIX1 reduces the expression of PTEN via activating PI3K/AKT signal to promote cell proliferation and tumorigenesis in osteosarcoma.

Biomed Pharmacother. 2018-5-26

[10]
Up-regulation of LINC00619 promotes apoptosis and inhibits proliferation, migration and invasion while promoting apoptosis of osteosarcoma cells through inactivation of the HGF-mediated PI3K-Akt signalling pathway.

Epigenetics. 2022

本文引用的文献

[1]
The Targeted Therapies for Osteosarcoma Six Major Pathways.

Curr Mol Pharmacol. 2024

[2]
Advances in Osteosarcoma.

Curr Osteoporos Rep. 2023-8

[3]
RING finger gene 180 inhibits osteosarcoma progression through regulating chromobox homolog 4 ubiquitination.

Cell Cycle. 2023-5

[4]
Inhibitor of apoptosis proteins as therapeutic targets in bladder cancer.

Front Oncol. 2023-2-10

[5]
Breast cancer heterogeneity and its implication in personalized precision therapy.

Exp Hematol Oncol. 2023-1-9

[6]
Cellular functions and molecular mechanisms of ubiquitination in osteosarcoma.

Front Oncol. 2022-12-1

[7]
A pan-cancer analysis of ring finger protein 135 and its relationship to triple-negative breast cancer proliferation and metastasis.

Aging (Albany NY). 2022-12-10

[8]
The PI3K/AKT signaling pathway in cancer: Molecular mechanisms and possible therapeutic interventions.

Exp Mol Pathol. 2022-8

[9]
RNF135 Promoter Methylation Is Associated With Immune Infiltration and Prognosis in Hepatocellular Carcinoma.

Front Oncol. 2022-1-25

[10]
Cullin-RING Ubiquitin Ligase Regulatory Circuits: A Quarter Century Beyond the F-Box Hypothesis.

Annu Rev Biochem. 2021-6-20

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