Front Oncol. 2020;10:1730
Authors: Li C, Ge M, Chen D, Sun T, Jiang H, Xie Y, Lu H, Zhang B, Han L, Chen J, Zhu J
Abstract
Background: Our previous study showed that the ribosomal protein L21 (RPL21) may play an important role in the development and survival of pancreatic cancer. In this article, RNA interference (RNAi) experiments were performed with RPL21-specific small interfering RNA (siRNA) to elucidate the mechanism by which RPL21 controls PC PANC-1 and BxPC-3 cell proliferation.
Methods: In the present study, PANC-1, BxPC-3 cells, and BALB/c nude mice were used to investigate antitumor effect and mechanism by which RPL21 controls cell proliferation and apoptosis in vitro and in vivo. The effects of RPL21 knockdown on PANC-1 and BxPC-3 cell proliferation, cell cycle and cell apoptosis in vitro were determined using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assays and flow cytometry assay. The mechanism of RPL21 regulating cell proliferation was investigated using transcriptome sequencing analysis and luciferase reporter assay. The effects of RPL21 knockdown on PANC-1 and BxPC-3 cell proliferation in vivo were determined using BALB/c nude mice tumor model.
Results: In PANC-1 and BxPC-3 cells, the knockdown of RPL21 expression with corresponding siRNA suppressed cell proliferation in vitro and in vivo, inhibited DNA replication, and induced arrests in the G1 phase of the cell cycle. Further results showed that the mini-chromosome maintenance (MCM) protein family (MCM2-7), CCND1 and CCNE1 were down-regulated significantly in PANC-1 and BxPC-3 cells after transfected with RPL21 siRNA, which suggests that the suppression of DNA replication is due to the reduced expression of MCM2-7 family, and the induction of G1 arrest is correlated with the inhibition of CCND1 and CCNE1. Luciferase reporter assay showed that RPL21 controls the DNA replication and G1-S phase progression possibly through the regulation of E2F1 transcription factor in PC cells. Moreover, RPL21 siRNA showed an apoptosis-inducing effect only in BxPC-3 and PANC-1 cells but not in normal HPDE6-C7 cells. The increase of caspase-8 activities and the loss of mitochondrial membrane potential after RPL21 silencing indicates that the RPL21 gene may be involved in caspase-8-related mitochondrial apoptosis.
Conclusion: Our findings suggest that siRNA against the RPL21 gene possesses a potential anti-cancer activity for PC cells by inhibiting their proliferation and DNA replication, as well as inducing cell cycle G1 arrest and cell apoptosis.
PMID: 33014855 [PubMed]
HDAC8: A Promising Therapeutic Target for Acute Myeloid Leukemia. Front Cell Dev Biol. 2020;8:844 Authors: Spreafico M, Gruszka AM, Valli D, Mazzola M, Deflorian G, Quintè A, Totaro MG, Battaglia C, Alcalay M, Marozzi A, Pistocchi A Abstract Histone deacetylase 8 (HDAC8), a class I HDAC that modifies non-histone proteins such as p53, is highly expressed in different hematological neoplasms including a subtype of acute myeloid leukemia...
Tue Oct 06, 2020 13:10
AMPK Activity Contributes to G2 Arrest and DNA Damage Decrease via p53/p21 Pathways in Oxidatively Damaged Mouse Zygotes. Front Cell Dev Biol. 2020;8:539485 Authors: He P, Li Z, Xu F, Ru G, Huang Y, Lin E, Peng S Abstract In zygotes, the capacity of G2/M checkpoint and DNA repair mechanisms to respond to DNA damage varies depending on different external stressors. In our previous studies, we found that mild oxidative stress induced a G2/M...
Tue Oct 06, 2020 13:10
Synthesis of Self-Targeted Carbon Dot with Ultrahigh Quantum Yield for Detection and Therapy of Cancer. ACS Omega. 2020 Sep 29;5(38):24628-24638 Authors: Azizi M, Valizadeh H, Shahgolzari M, Talebi M, Baybordi E, Dadpour MR, Salehi R, Mehrmohammadi M Abstract This study aims to engineer a new type of ultrahigh quantum yield carbon dots (CDs) from methotrexate (MTX-CDs) with self-targeting, imaging, and therapeutic effects on MDA-MB 231...
Tue Oct 06, 2020 13:10
OTX1 is a novel regulator of proliferation, migration, invasion and apoptosis in lung adenocarcinoma. Eur Rev Med Pharmacol Sci. 2020 Sep;24(18):9497-9510 Authors: Yang CY, Wang L, Mu DC, Li FF, Ran PZ, Shen H, Li WY, Ma J, Wu JH, Yang XR, Zheng SY Abstract OBJECTIVE: Orthodenticle Homeobox 1 (OTX1) has been found to be closely related to the development of several human tumours. However, the function and underlying molecular mechanisms...
Tue Oct 06, 2020 13:10
STAT3 gene polymorphism in chronic obstructive pulmonary disease. Eur Rev Med Pharmacol Sci. 2020 Sep;24(18):9618-9625 Authors: Wang J, Dai N, Cheng DH, Gao JY, Zheng JQ, Liu ZG Abstract OBJECTIVE: The aim of this study was to explore the correlation between rs8069115, rs41289087, and rs11079042 polymorphisms of the signal transducer and activator of transcription 3 (STAT3) gene and chronic obstructive pulmonary disease (COPD). ...
Tue Oct 06, 2020 13:10
Anthocyanins from Aronia melanocarpa Elliot induce apoptosis in Caco-2 cells through Wnt/β-catenin signaling pathway. Chem Biodivers. 2020 Oct 04;: Authors: Wei J, Yu W, Hao R, Fan J, Gao J Abstract Colorectal cancer (CRC) is one of the most common malignant tumors in the world. In this study, the Caco-2 in vitro cell model was used to study the effect and mechanism of Aronia melanocarpa Elliot anthocyanins (AMA) on colon cancer. The...
Tue Oct 06, 2020 13:10
CAVIN2 is frequently silenced by CpG methylation and sensitizes lung cancer cells to paclitaxel and 5-FU. Epigenomics. 2020 Oct 05;: Authors: Peng M, Ye L, Yang L, Liu X, Chen Y, Huang G, Jiang Y, Wang Y, Li D, He J, Qiu Z, Xiang T, Guo S Abstract Aim: To explore the biological functions and clinical significance of CAVIN2 in lung cancer. Materials & methods: Methylation-specific PCR was used to measure promoter methylation of CAVIN2....
Tue Oct 06, 2020 13:10
CDKN1B/p27 regulates autophagy via the control of Ragulator and MTOR activity in amino acid-deprived cells. Autophagy. 2020 Oct 04;: Authors: Nowosad A, Besson A Abstract The tumor suppressor CDKN1B/p27Kip1 binds to and inhibits cyclin-CDK complexes in the nucleus, inducing cell cycle arrest. However, when in the cytoplasm, CDKN1B may promote tumorigenesis. Notably, cytoplasmic CDKN1B was reported to promote macroautophagy/autophagy in...
Tue Oct 06, 2020 13:10
Suppression of multiple processes relevant to cancer progression by benzyl isothiocyanate may result from the inhibition of Aurora A kinase activity. Food Funct. 2020 Oct 05;: Authors: Yu TT, Chang MY, Hsieh YJ, Chang CJ Abstract Cruciferous vegetables are good sources of phytochemicals that have the potential to prevent cancer. Benzyl isothiocyanate (BITC) is the hydrolysis product of glucosinolates that are especially abundant in cruciferous...
Tue Oct 06, 2020 13:10
The synergistic proapoptotic effect of PARP-1 and HDAC inhibition in cutaneous T-cell lymphoma is mediated via Blimp-1. Blood Adv. 2020 Oct 13;4(19):4788-4797 Authors: Kruglov O, Wu X, Hwang ST, Akilov OE Abstract The therapy of advanced mycosis fungoides (MF) presents a therapeutic challenge, and the search for new therapeutic targets is ongoing. Poly(ADP-ribose) polymerase 1 was shown to be upregulated in patients with advanced MF and...
Tue Oct 06, 2020 13:10
RA-XII, a bicyclic hexapeptidic glucoside isolated from Rubia yunnanensis Diels, exerts antitumor activity by inhibiting protective autophagy and activating Akt-mTOR pathway in colorectal cancer cells. J Ethnopharmacol. 2020 Oct 02;:113438 Authors: Wang J, Wang J, Li L, Feng L, Wang YR, Wang Z, Tan NH Abstract ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Rubia yunnanensis Diels (Chinese name 'Xiao-Hong-Shen'), a traditional Chinese medicine...
Tue Oct 06, 2020 13:10
Superior inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation via cell cycle arrest and apoptosis: linking dietary fiber to cancer prevention. Nutr Res. 2020 Aug 22;83:63-72 Authors: Zeng H, Hamlin SK, Safratowich BD, Cheng WH, Johnson LK Abstract Intake of dietary fiber may protect against colon cancer. The anticancer property is associated with an increased production of short chain...
Tue Oct 06, 2020 13:10
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου