Upregulation of NETO2 gene in colorectal cancer

Fedorova, Maria S.; Snezhkina, Anastasiya V.; Pudova, Elena A.; Абрамов, И. С.; Lipatova, Anastasiya V.; Kharitonov, Sergey L.; Садритдинова, А. Ф.; Nyushko, K. M.; Klimina, Ksenia M.; Belyakov, M. M.; Slavnova, E. N.; Melnikova, Nataliya V.; Черниченко, М. А.; Сидоров, Д. В.; Kiseleva, Marina V.; Каприн, А. Д.; Alekseev, B. Ya.; Dmitriev, Alexey A.; Kudryavtseva, Anna V.

doi:10.1186/s12863-017-0581-8

Cited by 15 publications

(13 citation statements)

References 70 publications

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“…In our work, manipulation of NETO2 gene significantly changed not only the cell morphology but also the expression of mesenchymal and epithelial markers in GC cells, implying that induction of EMT was involved in NETO2-promoted invasion and metastasis of GC cells. However, Maria et al 34 reported that the elevated mRNA level of NETO2 in CRC was not directly correlated with expression of EMT-related genes. The reason for the discrepant results is not clear but may be may be attributed to the difference in tumor types.…”

Section: Discussionmentioning

confidence: 99%

NETO2 promotes invasion and metastasis of gastric cancer cells via activation of PI3K/Akt/NF-κB/Snail axis and predicts outcome of the patients

Liu

Jiang

et al. 2019

Cell Death Dis

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Aberrant expression of neuropilin and tolloid-like 2 (NETO2) has been observed during the progression of some human carcinomas. However, the expression pattern and clinical relevance of NETO2 in gastric cancer (GC) remain to be elucidated. In this study, we found that NETO2 expression was higher in GC tissues compared with paired non-cancerous tissues. Moreover, the expression of NETO2 was positively correlated with clinical stage, invasion depth, lymph node metastasis, and tumor size, but inversely correlated with overall and disease-free survival rates. Cox regression analysis identified NETO2 as an independent prognostic indicator for GC patients. Overexpression of NETO2 facilitated migration and invasion of GC cells in vitro and metastasis in vivo in association with induction of epithelial-mesenchymal transition. Conversely, knockdown of NETO2 had the opposite effects. Mechanistically, silencing NETO2 reduced the phosphorylation of PI3K, AKT, and NF-κB p65 as well as the expression of Snail, whereas NETO2 overexpression achieved the opposite results. Furthermore, we identified TNFRSF12A as a mediator for NETO2 to activate PI3K/AKT/NF-κB/Snail axis. Collectively, our results demonstrate that NETO2 promotes invasion and metastasis of GC cells and represents a novel prognostic indicator as well as a potential therapeutic target in GC.

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Section: Discussionmentioning

confidence: 99%

NETO2 promotes invasion and metastasis of gastric cancer cells via activation of PI3K/Akt/NF-κB/Snail axis and predicts outcome of the patients

Liu

Jiang

et al. 2019

Cell Death Dis

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“…Recent studies have shown that SMAD7 is present in common malignancies and acts as a tumor suppressor, including lung cancer, liver cancer, gastric cancer, bladder cancer, triple negative breast cancer, and osteosarcoma [11,[23][24][25][26][27][28]. In CRC, reduced level of SMAD7 is found to be involved in the process of cancer growth as well as the process of EMT and invasion [29]. Studies also show that SMAD7 gene polymorphisms are associated with CRC risk in patients with Lynch syndrome [30].…”

Section: Discussionmentioning

confidence: 99%

MiR-581/SMAD7 Axis Contributes to Colorectal Cancer Metastasis: A Bioinformatic and Experimental Validation-Based Study

Zhao

Liu

Yan

et al. 2020

IJMS

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Metastasis is a well-known poor prognostic factor and primary cause of mortality in patients with colorectal cancer (CRC). Recently, with the progress of high through-put sequencing, aberrantly expressed non-coding RNAs (ncRNAs) were found to participate in the initiation and development of cancer. However, the mechanisms of ncRNA-mediated regulation of metastasis in CRC remain largely unknown. In this study, we systematically analyzed the expression network of microRNAs (miRNAs) and genes in CRC metastasis using bioinformatics, and discovered that the miR-581/SMAD7 axis could be a potential factor that drives CRC metastasis. A dual luciferase report assay and protein analysis confirmed the binding relationship between miR-581 and SMAD7. Further functional assays revealed that miR-581 inhibition could suppress cell proliferation and induce apoptosis in SW480 cells. Up-regulation or down-regulation of miR-581 could both affect cell invasion capacity and modulate epithelial to mesenchymal transition (EMT) via a SMAD7/TGFβ signaling pathway. In conclusion, our findings elucidated that miR-581/SMAD7 could be essential for CRC metastasis, and may serve as a potential therapeutic target for CRC patients.

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“…Initial studies have mainly focused on its biological functions in neural-specific processes 7. However, subsequent reports have revealed that the expression of NETO2 is also found in several non-neural tissues, and recent studies have further indicated that NETO2 expression is associated with various cancers such as renal, lung, colon, cervical and colorectal cancer 8,9. In particular, a clinical study of the relationship between dysregulation of NETO2 expression and colorectal cancer progression has suggested that NETO2 upregulation is associated with poor prognosis and may function as a potential biomarker of advanced carcinoma progression 10.…”

Section: Introductionmentioning

confidence: 99%

NETO2 promotes pancreatic cancer cell proliferation, invasion and migration via activation of the STAT3 signaling pathway

Li¹,

Zhang²,

Liu³

2019

CMAR

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Purpose: The biological functions of neuropilin and tolloid-like 2 ( NETO2 ) in the progression of pancreatic cancer remained unexplored. We aimed to investigate the biological roles and underlying molecular mechanisms of NETO2 in pancreatic cancer. Materials and methods: Thirty paired pancreatic tumor tissue samples and corresponding nontumor tissues were obtained from 30 pancreatic cancer patients who did not receive preoperative chemotherapy or radiotherapy. The changes in multiple cellular functions associated with tumor progression were assessed after NETO2 knockdown/overexpression in pancreatic cancer cell lines. Additionally, a mouse-xenograft model was developed to verify the in vitro results. Results: NETO2 was upregulated in pancreatic tumor tissues. Elevated expression of NETO2 was not only associated with an advanced tumor stage, but was also a prediction of poor prognosis for pancreatic cancer patients. Knockdown of NETO2 in pancreatic cancer cell lines arrested the cell cycle and inhibited cell proliferation, colony formation, invasion, and migration; in contrast, overexpression of NETO2 had an opposite effect on all of these parameters. A STAT3 specific inhibitor, cryptotanshinone, reversed the tumor-promoting effects induced by NETO2 overexpression in pancreatic cancer. Western blot analysis showed that invasion and migration were closely related to epithelial–mesenchymal transition, and that the STAT3 signaling pathway was involved in NETO2 -mediated oncogenic transformation in pancreatic cancer cells. Furthermore, NETO2 knockdown significantly inhibited the growth of pancreatic tumor xenografts in nude mice. Conclusion: NETO2 has an important role in the progression and metastasis of pancreatic cancer and could serve as a novel candidate for targeted therapy of pancreatic cancer.

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Upregulation of NETO2 gene in colorectal cancer

Cited by 15 publications

References 70 publications

NETO2 promotes invasion and metastasis of gastric cancer cells via activation of PI3K/Akt/NF-κB/Snail axis and predicts outcome of the patients

NETO2 promotes invasion and metastasis of gastric cancer cells via activation of PI3K/Akt/NF-κB/Snail axis and predicts outcome of the patients

MiR-581/SMAD7 Axis Contributes to Colorectal Cancer Metastasis: A Bioinformatic and Experimental Validation-Based Study

<p><em>NETO2</em> promotes pancreatic cancer cell proliferation, invasion and migration via activation of the <em>STAT3</em> signaling pathway</p>

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