NCOA3 as a Critical Oncogene in Thyroid Cancer via Modulating Major Signaling Pathways

Abstract Nuclear Receptor Coactivator (NCOA3) enhances transcriptional activation of nuclear hormone receptors. This study was designed to explore the role of NCOA3 in thyroid cancer. Our data demonstrated that protein expression of NCOA3 was significantly upregulated in thyroid cancer tissues. NCOA3 knockdown inhibited cell proliferation and invasion, and induced cell cycle arrest and apoptosis in thyroid cancer. Conversely, ectopic expression of NCOA3 promoted cell proliferation and invasiveness in thyroid cancer. Mechanically, NCOA3 promotes thyroid cancer cell survival and invasiveness through modulating PI3K/AKT, MAPK and Wnt/β-catenin pathways. Collectively, these findings suggest that NCOA3 is critical in the initiation and development of thyroid cancer, and maybe a possible marker for prognostic and therapeutic.

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Downregulation of miR-140 is correlated with Poor Prognosis and Progression of Thyroid Cancer

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200724180742 ◽

2020 ◽

Vol 20 ◽

Author(s):

Qianqian Yu ◽

Wenhai Sun ◽

Hui Hua ◽

Yulian Chi ◽

Xiaomin Liu ◽

...

Keyword(s):

Cell Proliferation ◽

Thyroid Cancer ◽

Cox Regression ◽

Quantitative Polymerase Chain Reaction ◽

Migration And Invasion ◽

Kaplan Meier ◽

Potential Prognostic Factor ◽

Polymerase Chain ◽

Cancer Tissues

Background: The incidence of thyroid cancer is increasing rapidly and there is an urgent need to explore novel therapeutic targets for thyroid cancer. MiR-140 has been reported to affect the progression of various cancers, which makes it possible to play a role in thyroid cancer. This study aimed to investigate the expression and role of miR-140 in thyroid cancer. Methods: The expression of miR-140 was investigated by reverse transcription-quantitative polymerase chain reaction (qRT-PCR) in thyroid cancer tissues and cell lines. The prognostic value of miR-140 in thyroid cancer was evaluated by Kaplan-Meier survival and Cox regression. Moreover, effects of miR-140 on cell proliferation, migration, and invasion of thyroid cancer were investigated by CCK-8 and Transwell assay. Results: MiR-140 was downregulated in thyroid cancer tissues and cells, which correlated with TNM stage and lymph node metastasis of patients. Patients with low miR-140 expression had a shorter survival time compared with that in patients with high miR-140 expression. Furthermore, miR-140 acts as an independent factor for the prognosis of thyroid cancer. Overexpression of miR-140 inhibited cell proliferation, migration, and invasion of thyroid cancer. Conclusion: MiR-140 can serve as a potential prognostic factor for patients with thyroid cancer and suppress the progression of thyroid cancer, which provides new insight for the therapeutic target for thyroid cancer.

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Iodide- and Glucose-Handling Gene Expression Regulated by Sorafenib or Cabozantinib in Papillary Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-3023 ◽

2015 ◽

Vol 100 (5) ◽

pp. 1771-1779 ◽

Cited By ~ 10

Author(s):

Maomei Ruan ◽

Min Liu ◽

Qianggang Dong ◽

Libo Chen

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Signal Transduction ◽

Cell Proliferation ◽

Thyroid Cancer ◽

Western Blot ◽

Glucose Transporter ◽

Signal Transduction Pathways ◽

Papillary Thyroid ◽

Cycle Arrest

Abstract Context: The aberrant silencing of iodide-handling genes accompanied by up-regulation of glucose metabolism presents a major challenge for radioiodine treatment of papillary thyroid cancer (PTC). Objective: This study aimed to evaluate the effect of tyrosine kinase inhibitors on iodide-handling and glucose-handling gene expression in BHP 2-7 cells harboring RET/PTC1 rearrangement. Main Outcome Measures: In this in vitro study, the effects of sorafenib or cabozantinib on cell growth, cycles, and apoptosis were investigated by cell proliferation assay, cell cycle analysis, and Annexin V-FITC apoptosis assay, respectively. The effect of both agents on signal transduction pathways was evaluated using the Western blot. Quantitative real-time PCR, Western blot, immunofluorescence, and radioisotope uptake assays were used to assess iodide-handling and glucose-handling gene expression. Results: Both compounds inhibited cell proliferation in a time-dependent and dose-dependent manner and caused cell cycle arrest in the G0/G1 phase. Sorafenib blocked RET, AKT, and ERK1/2 phosphorylation, whereas cabozantinib blocked RET and AKT phosphorylation. The restoration of iodide-handling gene expression and inhibition of glucose transporter 1 and 3 expression could be induced by either drug. The robust expression of sodium/iodide symporter induced by either agent was confirmed, and 125I uptake was correspondingly enhanced. 18F-fluorodeoxyglucose accumulation was significantly decreased after treatment by either sorafenib or cabozantinib. Conclusions: Sorafenib and cabozantinib had marked effects on cell proliferation, cell cycle arrest, and signal transduction pathways in PTC cells harboring RET/PTC1 rearrangement. Both agents could be potentially used to enhance the expression of iodide-handling genes and inhibit the expression of glucose transporter genes.

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Tumor-Suppressive MicroRNA-708 Targets Notch1 to Suppress Cell Proliferation and Invasion in Gastric Cancer

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15179680859017 ◽

2018 ◽

Vol 26 (9) ◽

pp. 1317-1326 ◽

Cited By ~ 4

Author(s):

Xuyan Li ◽

Xuanfang Zhong ◽

Xiuhua Pan ◽

Yan Ji

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Quantitative Polymerase Chain Reaction ◽

Ectopic Expression ◽

Luciferase Reporter ◽

Mrna Levels ◽

Inverse Association ◽

Novel Target ◽

Cancer Tissues ◽

Proliferation And Invasion

Growing evidence has demonstrated that numerous microRNAs (miRNAs) may participate in the regulation of gastric carcinogenesis and progression. This phenomenon suggests that gastric cancer-related miRNAs can be identified as effective therapeutic targets for this disease. miRNA-708 (miR-708) has recently been reported to be aberrantly expressed in several types of cancer and contribute to carcinogenesis and progression. However, the expression level, biological roles, and underlying mechanisms of miR-708 in gastric cancer are poorly understood. Here we found that miR-708 was downregulated in gastric cancer tissues and cell lines. Downregulated miR-708 expression was significantly associated with lymphatic metastasis, invasive depth, and TNM stage. Further investigation indicated that ectopic expression of miR-708 prohibited cell proliferation and invasion in gastric cancer. Bioinformatics analysis showed that Notch1 was a potential target of miR-708. Notch1 was further confirmed as a direct target gene of miR-708 in gastric cancer by dual-luciferase reporter assay, reverse transcription quantitative polymerase chain reaction, and Western blot analysis. Furthermore, an inverse association was found between miR-708 and Notch1 mRNA levels in gastric cancer tissues. In addition, restored Notch1 expression rescued the inhibitory effects on gastric cancer cell proliferation and invasion induced by miR-708 overexpression. Our findings highlight the tumor-suppressive roles of miR-708 in gastric cancer and suggest that miR-708 may be investigated as a novel target for gastric cancer treatment.

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The Role of Cavin3 in the Progression of Lung Cancer and Its Mechanism

BioMed Research International ◽

10.1155/2020/6364801 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Gaozhong Sun ◽

Kewei Ni

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cancer Progression ◽

Tumor Formation ◽

Migration And Invasion ◽

Clinical Value ◽

Promote Cell Proliferation ◽

Cancer Tissues

Objective. The purpose of this study was to describe the role of Cavin3 in the progression of lung cancer and its underlying mechanism. Methods. Totally, 200 cases of lung cancer tissues and corresponding paracancer tissues were collected. Cavin3 expression in samples was determined by qRT-PCR, and the correlation with lung cancer stages as well as prognosis was statistically analyzed combined with matched clinical information. To investigate the mechanism of Cavin3 in lung cancer progression, firstly, Cavin3 was detected in lung cancer cell lines A549, PC9, and H520. Then, cells with stable Cavin3 overexpression and Cavin3 knockout were established to determine the effect of Cavin3 overexpression on the mammalian target of rapamycin (mTOR) signaling pathway. Subsequently, cells were harvested for cell proliferation, migration, and invasion assays in vitro, as well as nude mouse transplantation tumor experiment in vivo. Results. Cavin3 was seen to be highly expressed in cancer tissues. Statistical analysis with matched clinical data showed that Cavin3 as a prognostic indicator of lung cancer had important clinical value. In addition, it could be found that high expression of Cavin3 was able to promote cell proliferation, migration, and invasion and also potentiate tumor formation in vivo. Conclusion. Cavin3 was highly expressed in lung cancer, and it was capable to promote cell proliferation, invasion, and migration.

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RRS1 Promotes Retinoblastoma Cell Proliferation and Invasion via Activating the AKT/mTOR Signaling Pathway

BioMed Research International ◽

10.1155/2020/2420437 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Xuejing Yan ◽

Shen Wu ◽

Qian Liu ◽

Jingxue Zhang

Keyword(s):

Signaling Pathway ◽

Ribosome Biogenesis ◽

Regulatory Protein ◽

Ectopic Expression ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Retinoblastoma Cell ◽

Cycle Arrest ◽

Pathway Inhibition

Ribosome biogenesis regulatory protein homolog (RRS1) is a protein required for ribosome biogenesis. Recent studies have identified an oncogenic role of RRS1 in some cancers, whereas the involvement of RRS1 in retinoblastoma (RB) remains to be determined. In this study, we aimed to explore the role of RRS1 in RB. We found that the expression of RRS1 was increased in RB tissues and cells. Lentivirus-mediated RRS1 overexpression promoted the proliferation, growth, and invasion of RB cells. Opposite results were found in RRS1 knockdown cells. In addition, RRS1 silencing induced cell cycle arrest at the G1 phase and apoptosis in RB cells, while RRS1 ectopic expression exhibited the opposite effect. At the molecular level, RRS1 activated the AKT/mTOR signaling pathway, inhibition of which largely blunted the proliferation, growth, and invasion of RB cells. Our study suggests that RRS1 functions as an oncogene in RB through activating the AKT/mTOR signaling pathway.

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circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

10.21203/rs.2.23146/v1 ◽

2020 ◽

Author(s):

Qin Xu ◽

Bo Deng ◽

Manlin Li ◽

Yang Chen ◽

Li Zhuan

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Target Gene ◽

Circular Rnas ◽

Ovarian Cancer Cells ◽

Competing Endogenous Rnas ◽

Cancer Tissues

Abstract Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

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miR-495-3p Depresses Cell Proliferation and Migration By Down-Regulating HMGB1 in Colorectal Cancer

10.21203/rs.3.rs-663678/v1 ◽

2021 ◽

Author(s):

Zhang Jieling ◽

Li Kai ◽

Zheng Huifen ◽

Zhu Yiping

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Gene Assay ◽

And Migration ◽

Cancer Tissues

Abstract Background: MicroRNAs play an important role in the genesis and progression of tumors, including colorectal cancer (CRC), which has a high morbidity and mortality rate. In this research, the role of miR-495-3p and HMGB1 in CRC was investigated.Methods: We performed qRT-PCR to detect the expression of miR-495-3p in colorectal cancer tissues and cell lines. Functional experiments such as CCK-8 assay, EDU assay, Transwell assay and apoptosis assay were conducted to explore the effects of miR-495-3p on the proliferation, migration and apoptosis of CRC cells in vitro. Then, the use of database prediction, dual-luciferase reporter gene assay and functional experiments verified the role of miR-495-3p target gene HMGB1 in CRC. Finally, rescue experiments was performed to investigate whether overexpression of HMGB1 could reverse the inhibitory effect of miR-495-3p on CRC cell proliferation in vivo and in vitro.Results: miR-495-3p was down-regulated in colorectal cancer tissues and cell lines, and could inhibit the proliferation and migration of colorectal cancer cells, and promote cell apoptosis. The database prediction and dual-luciferase reporter gene assay showed that HMGB1 was the downstream target gene of miR-495-3p. We finally demonstrated that miR-495-3p inhibited CRC cell proliferation by targeting HMGB1 in vitro and in vivo.Conclusion: Our research shows that miR-495-3p inhibits the progression of colorectal cancer by down-regulating the expression of HMGB1, which indicates that miR-495-3p may become a potential therapeutic target for colorectal cancer.

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Lenvatinib Promotes the Antitumor Effects of Doxorubicin in Anaplastic Thyroid Cancer

10.21203/rs.3.rs-29005/v1 ◽

2020 ◽

Author(s):

Xi Su ◽

Jiaxin Liu ◽

Haihong Zhang ◽

Qingqing Gu ◽

Xinrui Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Thyroid Cancer ◽

Combination Therapy ◽

Cell Cycle Arrest ◽

Anaplastic Thyroid Cancer ◽

Antitumor Efficacy ◽

Potential Candidate ◽

Antitumor Effects ◽

Cycle Arrest

Abstract Background Anaplastic thyroid cancer (ATC) is a kind of rare thyroid cancer with very poor prognosis. It is one of the deadliest cancers in human due to the aggressive behavior and resistance to treatment. Doxorubicin has been approved in ATC treatment as a single agent, but monotherapy still shows no improvement of the total survival in advanced ATC. Lenvatinib was investigated with encouraging results in treating the patients with radioiodine-refractory differentiated thyroid cancer (DTC). However, antitumor efficacy of combination therapy with lenvatinib and doxorubicin remains largely unclear. Methods The antitumor efficacy of combination therapy with lenvatinib and doxorubicin on ATC cell proliferation and was assessed by the MTT assay and colony formation. Flow cytometry were employed to assess ATC cells’ apoptosis and cell cycle arrest in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Result Lenvatinib monotherapy was less effective than doxorubicin in treating ATC cell lines and xenografts model. The combination therapy of lenvatinib and doxorubicin significantly inhibited ATC cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest in compared to lenvatinib or doxorubicin monotherapy. Conclusion Lenvatinib promotes the antitumor effects of doxorubicin in ATC cell and xenografts model. Lenvatinib/doxorubicin combination may be a potential candidate therapeutic approach for ATC.

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circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

10.21203/rs.2.23146/v2 ◽

2020 ◽

Author(s):

Qin Xu ◽

Bo Deng ◽

Manlin Li ◽

Yang Chen ◽

Li Zhuan

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Target Gene ◽

Circular Rnas ◽

Ovarian Cancer Cells ◽

Competing Endogenous Rnas ◽

Cancer Tissues

Abstract Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

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