Mechanism of Notch1‑saRNA‑1480 reversing androgen sensitivity in human metastatic castration‑resistant prostate cancer.

Published on Jul 1, 2020in International Journal of Molecular Medicine3.098
· DOI :10.3892/IJMM.2020.4597
Libin Ma3
Estimated H-index: 3
(ZJU: Zhejiang University),
Kang Jiang1
Estimated H-index: 1
(ZJU: Zhejiang University)
+ 4 AuthorsGang Deng1
Estimated H-index: 1
(ZJU: Zhejiang University)
Sources
Abstract
The aim of the present study was to explore the mechanism by which Notch1‑small activating (sa)RNA restored androgen sensitivity in human metastatic castration‑resistant prostate cancer (CRPC). After transfection of Notch1‑saRNA‑1480 in PC3 cells, the expression of Notch1 and androgen receptor (AR) was investigated by reverse transcription quantitative PCR (RT‑qPCR) and western blotting. Furthermore, the protein expression level of vascular endothelial growth factor (VEGF) was measured. Then, flow cytometry was used to analyze the cell cycle and apoptosis after transfection. Moreover, the migration and invasion ability of PC3 cells were assessed by transwell assays. Then, angiogenesis experiments were conducted to analyze the abilities of PC3 cells to form blood vessels. Furthermore, in vivo experiments detected the antitumor activity of Notch1‑saRNA‑1480. The mRNA and protein expression levels of Notch1 were significantly increased after transfection, while the expression levels of AR and VEGF were decreased. After transfection, the cell cycle was arrested at the G0/G1 checkpoint. Notch1‑saRNA‑1480 significantly increased the proportion of apoptotic cells after transfection. In addition, transwell assay results showed that PC3 cell migration and invasion were inhibited. The total vessel length was significantly decreased based on angiogenesis experiments, which indicated that PC3 cell angiogenesis was inhibited. In vivo experiments showed that Notch1‑saRNA‑1480 could inhibit tumor growth and volume. The protein expression of Notch1, AR, VEGF receptor 2 (VEGFR2) and VEGF in tumor tissues was consistent with in vitro levels. Notch1‑saRNA‑1480 could significantly inhibit the proliferation of PC3 cells in vitro and the growth of tumors in vivo, which is associated with the inhibition of the AR and VEGF pathways.
📖 Papers frequently viewed together
3 Citations
5 Authors (Yan Huang, ..., Li Zhang)
3 Citations
References33
Newest
#1Mingde Zang (SJTU: Shanghai Jiao Tong University)H-Index: 10
#2Lei Hu (SJTU: Shanghai Jiao Tong University)H-Index: 12
Last. Bingya Liu (SJTU: Shanghai Jiao Tong University)H-Index: 51
view all 8 authors...
Abstract Gastric cancer is a great threat to the health of the people worldwide and lacks effective therapeutic regimens. Luteolin is one of Chinese herbs and presents in many fruits and green plants. In our previous study, we observed that luteolin inhibited cell migration and promoted cell apoptosis in gastric cancer. In the present study, luteolin significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) through decreasing cell migration and proliferation of HU...
33 CitationsSource
#1Wei Yu Chen (TMU: Taipei Medical University)H-Index: 15
#2Yuan Chin Tsai (TMU: Taipei Medical University)H-Index: 4
Last. Yen Nien Liu (TMU: Taipei Medical University)H-Index: 14
view all 8 authors...
Androgen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant prostate cancer after ADT. We identified the type 1, 2, and 4 collagen–binding protein transforming growth factor–β (TGFβ)–induced protein (TGFBI) as an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. In prostate cancer cell lines, AR...
34 CitationsSource
#1Arash Nabbi (U of C: University of Calgary)H-Index: 9
#2Urszula L. McClurg (Newcastle University)H-Index: 9
Last. Karl Riabowol (U of C: University of Calgary)H-Index: 52
view all 8 authors...
Abstract Background The androgen receptor (AR) is a major driver of prostate cancer, and increased AR levels and co-activators of the receptor promote the development of prostate cancer. INhibitor of Growth (ING) proteins target lysine acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of active transcription, to affect chromatin structure and gene expression. ING3 is a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated in prostate cancer de...
17 CitationsSource
#1Lianhua Zhang (SJTU: Shanghai Jiao Tong University)H-Index: 10
#2Jianjun Sha (SJTU: Shanghai Jiao Tong University)H-Index: 15
Last. Yiran Huang (SJTU: Shanghai Jiao Tong University)H-Index: 24
view all 6 authors...
ABSTRACTNotch signaling has been reported to play an essential role in tumorigenesis. Several studies have suggested that Notch receptors could be oncoproteins or tumor suppressors in different types of human cancers. Emerging evidence has suggested that Notch pathway regulates cell growth, apoptosis, cell cycle, and metastasis. In the current study, we explore whether Notch-1 could regulate the cell invasion and migration as well as EMT (epithelial-mesenchymal transition) in prostate cancer cel...
28 CitationsSource
#1Jingzhe Yang (PKU: Peking University)H-Index: 1
#2Chengli Wang (PKU: Peking University)H-Index: 1
Last. Tao Kong (PKU: Peking University)H-Index: 1
view all 7 authors...
: Prostate cancer is one of the most common malignancies in men, and it urgently demands precise interventions that target the signaling pathways implicated in its initiation, progression, and metastasis. The Notch-1 signaling pathway is closely associated with the pathophysiology of prostate cancer. This study investigated the antitumor effects and mechanisms of curcumin, which is a well-known natural compound from curcuminoids, in prostate cancer cells. Viability, proliferation, and migration ...
34 CitationsSource
Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistic...
10.4k CitationsSource
#1Tanya Stoyanova (Stanford University)H-Index: 19
#2Mireille Riedinger (UCLA: University of California, Los Angeles)H-Index: 11
Last. Owen N. Witte (UCLA: University of California, Los Angeles)H-Index: 119
view all 22 authors...
Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1...
26 CitationsSource
Purpose This review aims to summarize the evidence that Notch signaling is associated with prostate development, tumorigenesis and prostate tumor progression.
15 CitationsSource
#1Gang DengH-Index: 1
#2Xiang JuH-Index: 2
Last. Li‑Bin MaH-Index: 1
view all 5 authors...
Abstract The aim of the present study was to examine the anticarcinogenic effects of emodin on the Notch signaling pathway and vascular endothelial growth factor (VEGF) in the PC3 androgen-independent prostate cancer cell line in vitro. The cell viability was assessed using an 3‑(4,5)‑dimethylthiahiazo(‑z‑y1)‑3,5‑di‑phenytetrazolium bromide assay. Cell apoptosis and cell cycle were detected using flow cytometry. Morphological alterations were observed using transmission electron microscopy. The ...
15 CitationsSource
#1Thomas C. Roberts (University of Oxford)H-Index: 24
#2Jonathan R. Hart (Scripps Research Institute)H-Index: 21
Last. Kevin V. Morris (UNSW: University of New South Wales)H-Index: 47
view all 6 authors...
Roberts et al. describe how to measure transcriptional activity using nuclear run-on RT-qPCR assays. The approach is ideal for analyzing a single gene (or small number of genes) or for follow-up or validation of genome-wide analyses.
64 CitationsSource
Cited By1
Newest
#1Hossein GhanbarianH-Index: 16
#2Shahin AghamiriH-Index: 5
Last. Kay-Dietrich WagnerH-Index: 30
view all 5 authors...
Small double-strand RNA (dsRNA) molecules can activate endogenous genes via an RNA-based promoter targeting mechanism. RNA activation (RNAa) is an evolutionarily conserved mechanism present in diverse eukaryotic organisms ranging from nematodes to humans. Small activating RNAs (saRNAs) involved in RNAa have been successfully used to activate gene expression in cultured cells, and thereby this emergent technique might allow us to develop various biotechnological applications, without the need to ...
1 CitationsSource