PNO1 promotes cell proliferation in prostate cancer

Abstract BackgroundProstate cancer (PCa) is one of the most commonly diagnosed cancers. The functions of PNO1 in yeasts were involved in regulating ribosome and proteasome biogenesis. Human PNO1 is crucial to the site 3 cleavage at the 3ʹ-end of 18S pre-rRNA. Previous studies indicated that PNO1 may be related to the progression of cancers. However, the functions of PNO1 in PCa remained unclear. MethodsThe present study evaluated the expression levels of PNO1 in PCa by using GSE45016, GSE55945 and GSE17951 datasets. Then, in vivo and in vitro assays were conducted to detect the biological functions of PNO1 in PCa. Microarray and bioinformatic analysis were carried out to detect the downstream targets and pathways regulated by PNO1.ResultsThe present study for the first time demonstrated PNO1 was up-regulated in PCa samples compared to normal tissues. ShRNA mediated knockdown of PNO1 significantly suppressed PCa proliferation and clone formation, however, induced PCa apoptosis. Microarray analysis and bioinformatics analysis revealed PNO1 was involved in regulating multiple cancer related biological processes, such as regulation of DNA repair, single organismal cell-cell adhesion, translational initiation, RNA splicing, transcription, and positive regulation of mRNA catabolic process. OF note, in vivo results showed PNO1 knockdown remarkably reduced the PCa growth rate. ConclusionsDespite more in-depth research is still required, this study showed PNO1 could serve as a potential biomarker for PCa.

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PNO1 promotes cell proliferation in prostate cancer

10.21203/rs.2.17848/v1 ◽

2019 ◽

Author(s):

Jianpeng Hu ◽

Feilun Cui ◽

Zhipeng Xv ◽

Jian Tan ◽

Zhengyu Wang

Keyword(s):

Prostate Cancer ◽

Rna Splicing ◽

Bioinformatic Analysis ◽

In Vitro Assays ◽

Multiple Cancer ◽

Translational Initiation ◽

Normal Tissues ◽

Potential Biomarker

Abstract Background Prostate cancer (PCa) is one of the most commonly diagnosed cancers. The functions of PNO1 in yeasts were involved in regulating ribosome and proteasome biogenesis. However, its roles in PCa remained largely unclear. Methods The present study evaluated the expression levels of PNO1 in PCa by using GSE45016, GSE55945 and GSE17951 datasets. Then, in vivo and in vitro assays were conducted to detect the biological functions of PNO1 in PCa. BALB/c mice were used for in vivo assay in this study. Microarray and bioinformatic analysis were carried out to detect the downstream targets and pathways regulated by PNO1. Results The present study for the first time demonstrated PNO1 was up-regulated in PCa samples compared to normal tissues. ShRNA mediated knockdown of PNO1 significantly suppressed PCa proliferation and clone formation, however, induced PCa apoptosis. Microarray analysis and bioinformatics analysis revealed PNO1 was involved in regulating multiple cancer related biological processes, such as regulation of DNA repair, single organismal cell-cell adhesion, translational initiation, RNA splicing, transcription, and positive regulation of mRNA catabolic process. OF note, in vivo results showed PNO1 knockdown remarkably reduced the PCa growth rate. Conclusions Despite more in-depth research is still required, this study showed PNO1 could serve as a potential biomarker for PCa.

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PNO1 promotes cell proliferation in prostate cancer

10.21203/rs.2.17848/v3 ◽

2020 ◽

Author(s):

Jianpeng Hu ◽

Feilun Cui ◽

Zhipeng Xv ◽

Jian Tan ◽

Zhengyu Wang

Keyword(s):

Prostate Cancer ◽

Rna Splicing ◽

Biological Processes ◽

Multiple Cancer ◽

Translational Initiation ◽

Normal Tissues ◽

Potential Biomarker ◽

First Time ◽

Catabolic Process

Abstract Prostate cancer (PCa) is one of the most commonly diagnosed cancers. The functions of PNO1 in yeasts were involved in regulating ribosome and proteasome biogenesis. However, its roles in PCa remained largely unclear. The present study for the first time demonstrated PNO1 was up-regulated in PCa samples compared to normal tissues. ShRNA mediated knockdown of PNO1 significantly suppressed PCa proliferation and clone formation, however, induced PCa apoptosis. Microarray analysis and bioinformatics analysis revealed PNO1 was involved in regulating multiple cancer related biological processes, such as regulation of DNA repair, single organismal cell-cell adhesion, translational initiation, RNA splicing, transcription, and positive regulation of mRNA catabolic process. OF note, in vivo results showed PNO1 knockdown remarkably reduced the PCa growth rate. Despite more in-depth research is still required, this study showed PNO1 could serve as a potential biomarker for PCa.

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FAM64A Promotes Prostate Cancer Growth In Vivo and In Vitro

10.21203/rs.3.rs-33834/v1 ◽

2020 ◽

Author(s):

Feilun Cui ◽

Zhipeng Xu ◽

Yumei Lv ◽

Jianpeng Hu

Keyword(s):

Prostate Cancer ◽

Molecular Mechanisms ◽

Human Cancer ◽

Bioinformatic Analysis ◽

In Vitro Assays ◽

Multiple Cancer ◽

Cell Matrix ◽

Public Datasets

Abstract Background Prostate cancer (PCa) is the most common type of human cancer in males. However, the mechanisms underlying PCa tumorigenesis remained unclear.Methods The present study evaluated the expression levels of FAM64A in PCa by using 5 public datasets, including GSE8511, GSE45016, GSE55945, GSE38241 and GSE17951. Then, in vivo and in vitro assays were conducted to detect the biological functions of FAM64A in PCa. Microarray and bioinformatic analysis were carried out to detect the downstream targets and pathways regulated by FAM64A.Results In this study, we for first time demonstrate FAM64A as a biomarker for PCa. FAM64A was found to be overexpressed in PCa compared to normal samples. Higher FAM64A expression were found in Gleason score (GS) ≥ 8 PCa compared to GS < 8 PCa samples, in N1 staging compared to N1 staging PCa samples, and T3/4 staging compared to T1 staging PCa. Moreover, higher FAM64A expression was correlated to shorter survival time in PCa. Knockdown of FAM64A significantly suppressed PCa cell proliferation and colony formation, however, induced PCa apoptosis in vivo and in vitro. Bioinformatics analysis combined with microarray analysis revealed FAM64A played crucial roles in regulating multiple cancer related pathways, including cell-matrix adhesion and cAMP signaling pathway. Conclusions These results showed FAM64A could serve as a novel biomarker for PCa and will be helpful to understand the underlying FAM64A -related molecular mechanisms in the progression of PCa.

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The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.752573 ◽

2021 ◽

Vol 11 ◽

Author(s):

Dong Chen ◽

Yaqin Wang ◽

Feiya Yang ◽

Adili Keranmu ◽

Qingxin Zhao ◽

...

Keyword(s):

Prostate Cancer ◽

Real Time ◽

Expression Pattern ◽

Real Time Pcr ◽

Bioinformatic Analysis ◽

Biological Functions ◽

Quantitative Real Time Pcr ◽

Regulatory Effects

An increasing number of studies have shown that circRNAs are closely related to the carcinogenesis and development of prostate cancer (PCa). However, little is known about the effect of the biological functions of circRNAs on the enzalutamide resistance of PCa. Through bioinformatic analysis and experiments, we investigated the expression pattern of circRNAs in enzalutamide-resistant PCa cells. Quantitative real-time PCR was used to detect the expression of circRAB3IP, and plasmids that knock down or overexpress circRAB3IP were used to evaluate its effect on the enzalutamide sensitivity of PCa cells. Mechanistically, we explored the potential regulatory effects of eIF4A3 and LEF1 on the biogenesis of circRAB3IP. Our in vivo and in vitro data indicated that increased expression of circRAB3IP was found in enzalutamide-resistant PCa, and knockdown of circRAB3IP significantly enhanced enzalutamide sensitivity in PCa cells. However, upregulation of circRAB3IP resulted in the opposite effects. Further mechanistic research demonstrated that circRAB3IP could regulate the expression of serum and glucocorticoid-regulated kinase 1 (SGK1) by serving as a sponge that directly targets miR-133a-3p/miR-133b. Then, we showed that circRAB3IP partially exerted its biological functions via SGK1 signaling. Furthermore, we discovered that eIF4A3 and LEF1 might increase circRAB3IP expression in PCa.

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Targeting BC200/miR218-5p Signaling Axis for Overcoming Temozolomide Resistance and Suppressing Glioma Stemness

Cells ◽

10.3390/cells9081859 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1859 ◽

Cited By ~ 1

Author(s):

Yu-Kai Su ◽

Jia Wei Lin ◽

Jing-Wen Shih ◽

Hao-Yu Chuang ◽

Iat-Hang Fong ◽

...

Keyword(s):

Noncoding Rna ◽

Bioinformatic Analysis ◽

Benign Tumors ◽

Rna Expression ◽

Ki 67 ◽

Normal Tissues ◽

Significant Difference ◽

Signaling Axis

Background: Glioblastoma (GB) is one of the most common (~30%) and lethal cancers of the central nervous system. Although new therapies are emerging, chemoresistance to treatment is one of the major challenges in cancer treatment. Brain cytoplasmic 200 (BC200) RNA, also known as BCYRN1, is a long noncoding RNA (lncRNA) that has recently emerged as one of the crucial members of the lncRNA family. BC200 atypical expression is observed in many human cancers. BC200 expression is higher in invasive cancers than in benign tumors. However, the clinical significance of BC200 and its effect on GB multiforme is still unexplored and remains unclear. Methods: BC200 expression in GB patients and cell lines were investigated through RT-qPCR, immunoblotting, and immunohistochemistry analysis. The biological importance of BC200 was investigated in vitro and in vivo through knockdown and overexpression. Bioinformatic analysis was performed to determine miRNAs associated with BC200 RNA. Results: Our findings revealed that in GB patients, BC200 RNA expression was higher in blood and tumor tissues than in normal tissues. BC200 RNA expression have a statistically significant difference between the IDH1 and P53 status. Moreover, the BC200 RNA expression was higher than both p53, a prognostic marker of glioma, and Ki-67, a reliable indicator of tumor cell proliferation activity. Overexpression and silencing of BC200 RNA both in vitro and in vivo significantly modulated the proliferation, self-renewal, pluripotency, and temozolomide (TMZ) chemo-resistance of GB cells. It was found that the expressions of BC200 were up-regulated and that of miR-218-5p were down-regulated in GB tissues and cells. miR-218-5p inhibited the expression of BC200. Conclusions: This study is the first to show that the molecular mechanism of BC200 promotes GB oncogenicity and TMZ resistance through miR-218-5p expression modulation. Thus, the noncoding RNA BC200/miR-218-5p signaling circuit is a potential clinical biomarker or therapeutic target for GB.

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circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer

Molecular Cancer ◽

10.1186/s12943-019-1081-4 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 15

Author(s):

Sen Wang ◽

Dong Tang ◽

Wei Wang ◽

Yining Yang ◽

Xiaoqing Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Bioinformatic Analysis ◽

Migration And Invasion ◽

Circular Rnas ◽

Normal Tissues ◽

Tumour Metastasis ◽

Genome Wide ◽

Proliferation And Metastasis

Abstract Background As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. Methods circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. Results circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. Conclusion Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.

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Circular RNA _0008278 acts as a sponge of miR-378 and promotes proliferation and metastasis in gastric cancer

10.21203/rs.3.rs-335561/v1 ◽

2021 ◽

Author(s):

Xuan Li ◽

Haisheng Qian ◽

Hao Dong ◽

Yini Dang ◽

Lei Peng ◽

...

Keyword(s):

Gastric Cancer ◽

Bioinformatic Analysis ◽

Potential Method ◽

Circular Rna ◽

Migration And Invasion ◽

Normal Tissues ◽

Tumour Metastasis ◽

Regulatory Molecule

Abstract Background: Circular RNA (circRNA) is rising as an indispensable regulatory molecule in the progression of various kinds of malignant growth. However, little is known about the capacity and instruments of circRNA_0008727 in gastric cancer (GC). Our point was to recognize a novel circRNA-microRNA-mRNA useful system in gastric cancer. Method: CircRNA_0008278 was identified in three paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circRNA_0008278 combined with in vitro and in vivo assays were performed to prove the functional significance of circRNA_0008278. The molecular mechanism of circRNA_0008278 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments.Results: CircRNA_0008278 was frequently upregulated in GC tissues, and high circRNA_0008278 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circRNA_0008278 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, circRNA_0008278 over-expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circRNA_0008278 could sponge miR-378, thus indirectly regulating theYY1 expression and contributing to GC tumourigenesis.Conclusion: Our findings demonstrate that circRNA_0008278 functions as a tumour promoter in GC, and a new pathway circRNA_0008278/miR-378/YY1 which may be potential method for gastric cancer treatment.

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Stabilization of ADAM9 by N-α-acetyltransferase 10 protein contributes to promoting progression of androgen-independent prostate cancer

Cell Death and Disease ◽

10.1038/s41419-020-02786-2 ◽

2020 ◽

Vol 11 (7) ◽

Cited By ~ 2

Author(s):

Yung-Wei Lin ◽

Yu-Ching Wen ◽

Chih-Ying Chu ◽

Min-Che Tung ◽

Yi-Chieh Yang ◽

...

Keyword(s):

Prostate Cancer ◽

Metastatic Cancer ◽

Feedback Regulation ◽

Metastatic Potential ◽

Normal Tissues ◽

Tumor Growth And Metastasis ◽

Cancer Tissues ◽

Androgen Independent

Abstract N-α-Acetyltransferase 10 protein (Naa10p) was reported to be an oncoprotein in androgen-dependent prostate cancer (PCa; ADPC) through binding and increasing transcriptional activity of the androgen receptor (AR). PCa usually progresses from an androgen-dependent to an androgen-independent stage, leading to an increase in the metastatic potential and an incurable malignancy. At present, the role of Naa10p in androgen-independent prostate cancer (AIPC) remains unclear. In this study, in silico and immunohistochemistry analyses showed that Naa10 transcripts or the Naa10p protein were more highly expressed in primary and metastatic PCa cancer tissues compared to adjacent normal tissues and non-metastatic cancer tissues, respectively. Knockdown and overexpression of Naa10p in AIPC cells (DU145 and PC-3M), respectively, led to decreased and increased cell clonogenic and invasive abilities in vitro as well as tumor growth and metastasis in AIPC xenografts. From the protease array screening, we identified a disintegrin and metalloprotease 9 (ADAM9) as a potential target of Naa10p, which was responsible for the Naa10p-induced invasion of AIPC cells. Naa10p can form a complex with ADAM9 to maintain ADAM9 protein stability and promote AIPC’s invasive ability which were independent of its acetyltransferase activity. In contrast to the Naa10p-ADAM9 axis, ADAM9 exerted positive feedback regulation on Naa10p to modulate progression of AIPC in vitro and in vivo. Taken together, for the first time, our results reveal a novel cross-talk between Naa10p and ADAM9 in regulating the progression of AIPC. Disruption of Naa10p–ADAM9 interactions may be a potential intervention for AIPC therapy.

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miR-1272 Exerts Tumor-Suppressive Functions in Prostate Cancer via HIP1 Suppression

Cells ◽

10.3390/cells9020435 ◽

2020 ◽

Vol 9 (2) ◽

pp. 435

Author(s):

Federica Rotundo ◽

Denis Cominetti ◽

Rihan El Bezawy ◽

Stefano Percio ◽

Valentina Doldi ◽

...

Keyword(s):

Prostate Cancer ◽

Functional Characterization ◽

Developed Countries ◽

Membrane Turnover ◽

Normal Tissues ◽

Treat Prostate Cancer

The development of novel therapies or the improvement of currently used approaches to treat prostate cancer (PCa), the most frequently diagnosed male tumor in developed countries, is an urgent need. In this regard, the functional characterization of microRNAs, molecules shown to regulate a number of cancer-related pathways, is instrumental to their possible clinical exploitation. Here, we demonstrate the tumor-suppressive role of the so far uncharacterized miR-1272, which we found to be significantly down-modulated in PCa clinical specimens compared to normal tissues. Through a gain-of-function approach using miRNA mimics, we showed that miR-1272 supplementation in two PCa cell models (DU145 and 22Rv1) reverted the mesenchymal phenotype by affecting migratory and invasive properties, and reduced cell growth in vitro and in vivo in SCID mice. Additionally, by targeting HIP1 encoding the endocytic protein HIP1, miR-1272 balanced EGFR membrane turnover, thus affecting the downstream AKT/ERK pathways, and, ultimately, increasing PCa cell response to ionizing radiation. Overall, our results show that miR-1272 reconstitution can affect several tumor traits, thus suggesting this approach as a potential novel therapeutic strategy to be pursued for PCa, with the multiple aim of reducing tumor growth, enhancing response to radiotherapy and limiting metastatic dissemination.

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Long non-coding RNA HCG18 promotes malignant phenotypes of breast cancer (BC) cells by HCG18/miR-103a-3p/UBE2O/mTORC1/HIF-1α positive feedback loop

10.21203/rs.3.rs-241505/v1 ◽

2021 ◽

Author(s):

Xu Liu ◽

Kun Qiao ◽

Kaiyuan Zhu ◽

Xianglan Li ◽

Chunbo Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Positive Feedback ◽

Feedback Loop ◽

Bioinformatic Analysis ◽

In Vitro Assays ◽

Luciferase Reporter ◽

Regulatory Relationship ◽

Positive Feedback Loop

Abstract Background: In recent years, a growing number of studies have reported that long non-coding RNAs (LncRNAs) play crucial roles in breast cancer (BC) progression and metastasis. Another study group of our research center reported that LncRNA HCG18 was one of the 30 upregulated lncRNAs in BC tissues related to normal tissues in TCGA database. However, the exactly biological roles of HCG18 in BC remains unclear. Method: qRT-PCR was used to detect the expression profile of HCG18 in BC tissues and cell lines. In vitro assays were used to evaluate the pro-tumor function of HCG18 in BC cells. Animal study were used to explore the role of HCG18 in vivo. Bioinformatic analysis, dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and Chromatin Immunoprecipitation (ChIP) assays were used to investigate the regulatory relationship of HCG18, miR-103a-3p, UBE2O in BC. Results: HCG18 was upregulated in BC tissues and cells, and BC patients with high HCG18 expression tended to have poor prognosis. HCG18 could promote BC cells proliferation, invasion and provided BC cells with tumor stemness properties (CSPs) in vitro and facilitate tumor growth and lung metastasis in vivo. In terms of mechanism, HCG18 functioned as a miRNA sponge which positively regulated the expression of Ubiquitin-conjugating enzyme E2O (UBE2O) by sponging miR-103a-3p and our previous research achievement have already verified UBE2O could promote malignant phenotypes of BC cells through UBE2O/AMPKα2/mTORC1 axis. Furthermore, as a downstream target of HCG18/miR-103a-3p/UBE2O/mTORC1 axis, HIF-1α transcriptionally promoted HCG18 expression and then formed a positive feedback loop in BC. Conclusion: HCG18 played an oncogenic role in BC and it might serve as a prognostic biomarker and a potential therapeutic target for BC treatment.

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