ID2 Inhibits Bladder Cancer Progression and Metastasis via PI3K/AKT Signaling Pathway

Background: Inhibitors of DNA-binding (ID) proteins are important regulators of cell proliferation and differentiation. The aim of this study was to evaluated the role of ID proteins in bladder cancer (BCa) and related molecular mechanisms.Methods: The TCGA database was analyzed for the expression and clinical significance of ID proteins. The expression of ID2 was determined by qRT-PCR, immunohistochemical staining and western blot. The role of ID2 was determined by CCK-8, colony formation, wound healing, transwell and xenograft tumor assays, and the potential mechanism of ID2 in BCa was investigated by RNA sequencing.Results: ID2 expression was significantly downregulated in TCGA database and clinical samples, and high ID2 expression was associated with low-grade tumor staging and correlated with better overall survival, disease specific survival (DSS) and progress free interval (PFI). In vivo and in vitro experiments showed that knockdown of ID2 promoted proliferation, migration, invasion and metastasis of BCa cells, while overexpression of ID2 significantly inhibited cell proliferation, migration, invasion and metastasis. Mechanistically, ID2 acts as a tumor suppressor through PI3K/AKT signaling pathway to inhibit the progression and metastasis of BCa.Conclusion: Our results suggest that ID2 exerts tumor suppressive effects in BCa through PI3K/AKT signaling pathway, and altered ID2 expression can be used as a biomarker of BCa progression and metastasis.

Download Full-text

Overexpression of long non-coding RNA LINC00982 suppresses cell proliferation and tumor growth of papillary thyroid carcinoma through PI3K-ATK signaling pathway

Bioscience Reports ◽

10.1042/bsr20191210 ◽

2019 ◽

Vol 39 (7) ◽

Cited By ~ 1

Author(s):

Debin Xu ◽

Jichun Yu ◽

Shimin Zhuang ◽

Shuyong Zhang ◽

Zhengdong Hong ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Expression Levels ◽

And Migration ◽

Proliferation And Migration

Abstract Long non-coding RNAs (lncRNAs) have been widely reported that involved in human cancers, including papillary thyroid carcinoma (PTC). The present study aims to investigate the biological role of LINC00982 in PTC. The mRNA expression of LINC00982 in human PTC tissues was detected using qPCR. Moreover, Kaplan–Meier method was performed to analyze the internal relevance between LINC00982 expression and overall survival (OS) rate of patients with PTC. In addition, gain- and loss-of-functions assays were performed to detect the effects of LINC00982 on the cell proliferation and migration in PTC cells. Furthermore, western blot assay was used to measure the alteration expression levels of apoptosis relative proteins and the relative protein involved phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Finally, a xenograft model was used to analyze the antitumor role of LINC00982 in vivo. Here, we found that LINC00982 was decreased in human PTC tissues. Patients with decreased LINC00982 expression levels had a reduced OS (P=0.0019) compared with those with high LINC00982 expression levels. Overexpression of LINC00982 suppressed the proliferation and migration of BHT101 and B-CPAP cells and promoted cell apoptosis. Knockdown of LINC00982 promoted the proliferation and migration of BHT101 and B-CPAP cells and induced cell apoptosis. Moreover, in vivo assay showed that overexpression of LINC00982 could suppress the growth of PTC. Finally, LINC00982 could regulate the activity of PI3K/AKT signaling pathway in vitro and in vivo. Taken together, our findings demonstrated that overexpression of LINC00982 could suppress cell proliferation and induce cell apoptosis by regulating PI3K/AKT signaling pathway in PTC.

Download Full-text

Knockdown of UBE2T Inhibits Osteosarcoma Cell Proliferation, Migration, and Invasion by Suppressing the PI3K/Akt Signaling Pathway

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504016x14685034103310 ◽

2016 ◽

Vol 24 (5) ◽

pp. 361-369 ◽

Cited By ~ 17

Author(s):

Yu Wang ◽

Hui Leng ◽

Hui Chen ◽

Lei Wang ◽

Nan Jiang ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Akt Signaling ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Akt Signaling Pathway ◽

Inhibitory Effects ◽

Study Results ◽

Ubiquitin Conjugating Enzyme

Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the E2 family, was found to be overexpressed in a great many cancers such as bladder cancer, lung cancer, and prostate cancer. However, there have been no reports on the role of UBE2T in osteosarcoma. In this study, we tried to make the effects of UBE2T on osteosarcoma clear. The study results showed that UBE2T was overexpressed in osteosarcoma tissues and cell lines. Moreover, UBE2T knockdown inhibited osteosarcoma cell proliferation, migration, and invasion. We also observed that UBE2T downregulation could suppress the activity of the PI3K/Akt signaling pathway. Therefore, we concluded that UBE2T exerted its inhibitory effects on osteosarcoma cells via suppressing the PI3K/Akt signaling pathway. These findings indicated that UBE2T may be a potential therapeutic target for osteosarcoma treatment.

Download Full-text

E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability

Cell Death and Disease ◽

10.1038/s41419-021-03521-1 ◽

2021 ◽

Vol 12 (3) ◽

Author(s):

Huimin Xu ◽

Lingao Ju ◽

Yaoyi Xiong ◽

Mengxue Yu ◽

Fenfang Zhou ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Signaling Pathway ◽

Cancer Progression ◽

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

Akt Signaling ◽

Tumor Formation ◽

Akt Signaling Pathway

AbstractE3 ubiquitin ligase RNF126 (ring finger protein 126) is highly expressed in various cancers and strongly associated with tumorigenesis. However, its specific function in bladder cancer (BCa) is still debatable. Here, we found that RNF126 was significantly upregulated in BCa tissue by TCGA database, and our studies indicated that downregulation of RNF126 significantly inhibited cell proliferation and metastasis through the EGFR/PI3K/AKT signaling pathway in BCa cells. Furthermore, we identified PTEN, an inhibitor of the PI3K/AKT signaling pathway, as a novel substrate for RNF126. By co-immunoprecipitation assays, we proved that RNF126 directly interacts with PTEN. Predominantly, PTEN binds to the C-terminal containing the RING domain of RNF126. The in vivo ubiquitination assay showed that RNF126 specifically regulates PTEN stability through poly-ubiquitination. Furthermore, PTEN knockdown restored cell proliferation, metastasis, and tumor formation of BCa cells inhibited by RNF126 silencing in vitro and in vivo. In conclusion, these results identified RNF126 as an oncogene that functions through ubiquitination and degradation of PTEN in BCa.

Download Full-text

CTHRC1 facilitates bladder cancer cell proliferation and invasion through regulating the PI3K/Akt signaling pathway

Archives of Medical Science ◽

10.5114/aoms.2019.85718 ◽

2019 ◽

Author(s):

Yubing Li ◽

Xiangdong Cheng ◽

Jiasheng Yan ◽

Shaobo Jiang

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Signaling Pathway ◽

Cancer Cell ◽

Akt Signaling ◽

Bladder Cancer Cell ◽

Cancer Cell Proliferation ◽

Akt Signaling Pathway ◽

Proliferation And Invasion

Download Full-text

Orai1 Channel Regulates Human-Activated Pancreatic Stellate Cell Proliferation and TGFβ1 Secretion through the AKT Signaling Pathway

Cancers ◽

10.3390/cancers13102395 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2395

Author(s):

Silviya Radoslavova ◽

Antoine Folcher ◽

Thibaut Lefebvre ◽

Kateryna Kondratska ◽

Stéphanie Guénin ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Transforming Growth Factor ◽

Stellate Cell ◽

Akt Signaling ◽

Pancreatic Stellate Cells ◽

Proliferative Potential ◽

Akt Signaling Pathway ◽

Pancreatic Stellate Cell

Activated pancreatic stellate cells (aPSCs), the crucial mediator of pancreatic desmoplasia, are characterized, among others, by high proliferative potential and abundant transforming growth factor β1 (TGFβ1) secretion. Over the past years, the involvement of Ca2+ channels in PSC pathophysiology has attracted great interest in pancreatic cancer research. We, thus, aimed to investigate the role of the Orai1 Ca2+ channel in these two PSC activation processes. Using the siRNA approach, we invalided Orai1 expression and assessed the channel functionality by Ca2+ imaging, the effect on aPSC proliferation, and TGFβ1 secretion. We demonstrated the functional expression of the Orai1 channel in human aPSCs and its implication in the store-operated Ca2+ entry (SOCE). Orai1 silencing led to a decrease in aPSC proliferation, TGFβ1 secretion, and AKT activation. Interestingly, TGFβ1 induced a higher SOCE response by increasing Orai1 mRNAs and proteins and promoted both AKT phosphorylation and cell proliferation, abolished by Orai1 silencing. Together, our results highlight the role of Orai1-mediated Ca2+ entry in human aPSC pathophysiology by controlling cell proliferation and TGFβ1 secretion through the AKT signaling pathway. Moreover, we showed a TGFβ1-induced autocrine positive feedback loop by promoting the Orai1/AKT-dependent proliferation via the stimulation of Orai1 expression and function.

Download Full-text

Loss of IGF2R indicates a poor prognosis and promotes cell proliferation and tumorigenesis in bladder cancer via AKT signaling pathway

Neoplasma ◽

10.4149/neo_2019_190206n108 ◽

2020 ◽

Vol 67 (01) ◽

pp. 129-136 ◽

Cited By ~ 1

Author(s):

S. B. Liu ◽

L. B. Zhou ◽

H. F. Wang ◽

G. Li ◽

Q. P. Xie ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Signaling Pathway ◽

Poor Prognosis ◽

Akt Signaling ◽

Akt Signaling Pathway

Download Full-text

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666201005143818 ◽

2020 ◽

Vol 20 ◽

Author(s):

Md. Junaid ◽

Yeasmin Akter ◽

Syeda Samira Afrose ◽

Mousumi Tania ◽

Md. Asaduzzaman Khan

Keyword(s):

Clinical Trials ◽

Signaling Pathways ◽

Signaling Pathway ◽

Inhibitory Effect ◽

Akt Signaling ◽

Review Article ◽

Therapeutic Drug ◽

Akt Signaling Pathway ◽

Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

Download Full-text