PRR11 Is a Prognostic Marker and Potential Oncogene in Patients with Gastric Cancer

Song, Zigen; Liu, Wenying; Xiao, Yu; Zhang, Minghui; Luo, Yan; Yuan, Weiwei; Xu, Yu; Yu, Guanzhen; Hu, Yun

doi:10.1371/journal.pone.0128943

Cited by 42 publications

(49 citation statements)

References 24 publications

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“…Through regulating important genes involved in cell cycles and tumorigenesis, PRR11 participates in the initiation and progression of lung cancer and epithelial-to-mesenchymal transition in breast cancer [11]. Our previous research showed that PRR11 widely activated in human gastric cancer, and was an independent prognostic factor for gastric cancer patients, which are consistent with the hypothesis that PRR11 functions as an oncogene in the development and progression of gastric cancer [12]. However, whether an increase in PRR11 expression is responsible for the expansion of gastric CSC populations is not known.…”

Section: Introductionsupporting

confidence: 79%

“…Real-time quantitative PCR reaction was performed using SYBR1 Premix Ex TaqTM kit (Takara, Kyoto, Japan) according to the manufacturer's instructions and conventional PCR assays were performed using previously described method [12]. GAPDH was used as an internal standard.…”

Section: Rna Extraction and Real-time Pcrmentioning

confidence: 99%

“…GAPDH was used as an internal standard. The PCR cycle was performed according to previously published protocol [12]. Reactions and analysis were performed using the ABI PRISM 7300 PCR and detection system (Applied Biosystems, Carlsbad, CA).…”

Section: Rna Extraction and Real-time Pcrmentioning

confidence: 99%

“…We previously reported that PRR11 was highly expressed in gastric tumor tissues, and played important roles in tumor progression [12]. However, its role in gastric CSCs is unknown.…”

Section: Prr11 Was Highly Expressed In Gastric Cscsmentioning

confidence: 99%

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Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells

Hu¹,

Song²,

Yao³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Gastric cancer is a highly aggressive tumor containing cancer stem cells (CSCs), which participate in tumor initiation, therapeutic resistance, and tumor relapse. Proline-rich protein 11 (PRR11) has been shown to be up-regulated in human cancers; however, its role in gastric CSCs is unknown. We hypothesize that PRR11 may affect tumorigenicity of gastric CSCs. In this study, we explored the biological function and regulation of PRR11 in gastric CSCs. Methods: Expression of PRR11 was evaluated in gastric CSC cell line by real-time quantitative PCR and western blot. The effect of PRR11 on tumorigenicity was examined by interference with gene expression using lentiviral vector-loaded shRNA. A xenograft tumor model using NOD/SCID mice was established to examine the role of PRR11 in tumor development. Results: Data showed that PRR11 was highly expressed in gastric CSCs. PRR11 was responsible for the maintenance of self-renewal and tumorigenicity of gastric CSCs, and overexpression of exogenous PRR11 could restore the self-renewal of gastric non-CSCs. Furthermore, interference with PRR11 altered the expression of stemness transcription factors. Interestingly, MAPK signaling controlled PRR11 expression by increasing PRR11 protein stability, and maintained gastric CSCs self-renewal in a PRR11 dependent manner. Conclusions: PRR11 regulated self-renewal and tumorigenicity of gastric CSCs through MAPK signaling, and could be used as a therapeutic target for gastric cancer.

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Section: Introductionsupporting

confidence: 79%

Section: Rna Extraction and Real-time Pcrmentioning

confidence: 99%

Section: Rna Extraction and Real-time Pcrmentioning

confidence: 99%

“…We previously reported that PRR11 was highly expressed in gastric tumor tissues, and played important roles in tumor progression [12]. However, its role in gastric CSCs is unknown.…”

Section: Prr11 Was Highly Expressed In Gastric Cscsmentioning

confidence: 99%

See 2 more Smart Citations

Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells

Hu¹,

Song²,

Yao³

et al. 2018

Cell Physiol Biochem

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“…Specific short hairpin RNA-mediated depletion of PRR11 causes cell cycle arrest, leading to a significant decrease in cell viability [7]. PRR11 has been regarded as a potential new target for the diagnosis and treatment of lung cancer, as it regulates key genes associated with tumor occurrence [8,9]. However, despite growing evidence demonstrating that PRR11 is as an important cancer-related protein, the role of PRR11 in OC and the underlying molecular mechanisms have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

PRR11 Overexpression Facilitates Ovarian Carcinoma Cell Proliferation, Migration, and Invasion Through Activation of the PI3K/AKT/β-Catenin Pathway

Zhu

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ovarian cancer (OC) is the most lethal gynecologic malignancy, mainly due to the advanced stage at diagnosis in most patients and high rate of relapse. Thus, it is still essential to elucidate the underlying mechanisms and explore the diagnostic and therapeutic targets of OC. Recent studies have revealed that proline-rich protein 11 (PRR11) is dysregulated in different cancers, participating in their initiation and progression; however, it remains unclear whether PRR11 is involved in OC. Methods: Immunohistochemical staining, quantitative reverse transcription PCR, and western blotting were performed to evaluate PRR11 expression in OC tissues and cells. The relationship between PRR11 expression and the clinicopathologic data of patients were analyzed. We upregulated and downregulated PRR11 expression using a PRR11 overexpression vector and PRR11-specifc small interfering RNA, respectively, to further clarify its role in the malignant biological behavior of OC in vitro. Results: Overexpression of PRR11 in OC tissues and cells significantly correlated with advanced FIGO stage, lymph node metastasis, and large tumor size. Downregulation of PRR11 inhibited cell proliferation and prevented the invasion and migration of HO-8910 OC cells, whereas opposite results were observed in Caov3 cells upon PRR11 upregulation. Further analyses showed that PRR11 positively regulated cell proliferation-related proteins, including c-myc and cyclin D1, and increased and decreased the expression of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2, respectively. Additionally, our preliminary results demonstrated that PRR11 expression was mediated by the phosphoinositide 3-kinase/AKT/β-catenin signaling pathway. Conclusion: The results of this study provide evidence that PRR11 plays a critical role in the progression and metastasis of OC, and as such, may serve as a potential prognostic and therapeutic target in OC.

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PRR11 unveiled as a top candidate biomarker within the RBM3‐regulated transcriptome in pancreatic cancer

Hau

Wahlin

Cervin

et al. 2021

The Journal of Pathology CR

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The outlook for patients with pancreatic cancer remains dismal. Treatment options are limited and chemotherapy remains standard of care, leading to only modest survival benefits. Hence, there is a great need to further explore the mechanistic basis for the intrinsic therapeutic resistance of this disease, and to identify novel predictive biomarkers. RNA-binding motif protein 3 (RBM3) has emerged as a promising biomarker of disease severity and chemotherapy response in several types of cancer, including pancreatic cancer. The aim of this study was to unearth RBM3-regulated genes and proteins in pancreatic cancer cells in vitro, and to examine their expression and prognostic significance in human tumours. Next-generation RNA sequencing was applied to compare transcriptomes of MIAPaCa-2 cells with and without RBM3 knockdown. The prognostic value of differentially expressed genes (DEGs) was examined in The Cancer Genome Atlas (TCGA). Top deregulated genes were selected for further studies in vitro and for immunohistochemical analysis of corresponding protein expression in tumours from a clinically well-annotated consecutive cohort of 46 patients with resected pancreatic cancer. In total, 19 DEGs (p < 0.01) were revealed, among which some with functions in cell cycle and cell division stood out; PDS5A (PDS cohesin associated factor A) as the top downregulated gene, CCND3 (cyclin D3) as the top upregulated gene, and PRR11 (proline rich 11) as being highly prognostic in TCGA. Silencing of RBM3 in MiaPaCa-2 cells led to congruent alterations of PDS5A, cyclin D3, and PRR11 levels. High protein expression of PRR11 was associated with adverse clinicopathological features and shorter overall survival. Neither PDS5A nor cyclin D3 protein expression was prognostic. This study unveils several RBM3-regulated genes with potential clinical relevance in pancreatic cancer, among which PRR11 shows the most consistent association with disease severity, at both transcriptome and protein levels.

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PRR11 Is a Prognostic Marker and Potential Oncogene in Patients with Gastric Cancer

Cited by 42 publications

References 24 publications

Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells

Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells

PRR11 Overexpression Facilitates Ovarian Carcinoma Cell Proliferation, Migration, and Invasion Through Activation of the PI3K/AKT/β-Catenin Pathway

PRR11 unveiled as a top candidate biomarker within the RBM3‐regulated transcriptome in pancreatic cancer

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