Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem cells

Song, Wen-Shin; Yang, Yi‐Ping; Huang, Cheng-Yang; Lu, Kai-Hsi; Liu, Wei-Hsiu; Wu, Wai-Wah; Lee, Yi-Yen; Lo, Wen-Liang; Lee, Shou‐Dong; Chen, Yiwei; Huang, Pin I.; Chen, Ming-Teh

doi:10.1016/j.jcma.2016.03.010

Cited by 88 publications

(81 citation statements)

References 38 publications

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“…SOX genes have been demonstrated to be associated with the differentiation and proliferation of cells (30), and have oncogene functions (31,32). It is reported that SOX10 and SOX1 are tumor-associated antigens of melanoma and small cell lung cancer cells, respectively (33,34).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑138 inhibits SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells

Zhu

Jin

2018

Exp Ther Med

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The aim of the present study was to investigate the expression and biological functions of microRNA (miR)-138 in ovarian cancer at the tissue and cellular levels, as well as its underlying mechanisms. A total of 47 patients with ovarian cancer were included in the present study. Ovarian cancer tissues were subjected to staging classification according to the FIGO 2000 criteria. Lymphatic metastasis was also examined. Ovarian cancer A2780 cells were transfected using liposomes. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of miR-138. A Cell-Counting Kit 8 assay was used to examine cell viability, while a Transwell assay was employed to study cell invasion and migration. The effects of miR-138 on SOX12 protein expression were examined by western blot analysis. A dual luciferase reporter assay was performed to identify the direct interaction between miR-138 and SOX12 gene. Expression of miR-138 was downregulated in ovarian cancer tissues. The level of miR-138 in patients with ovarian cancer with lymphatic metastasis was significantly lower compared with patients without lymphatic metastasis. However, expression of miR-138 was not associated with the stage of ovarian cancer. Upregulation of miR-138 inhibited the proliferation and suppressed the invasion and migration of A2780 cells. SOX12 promoted the proliferation, invasion and migration of A2780 cells. In addition, miR-138 downregulated the expression of SOX12 via binding with the 3′-UTR of SOX12 gene. The present study demonstrates that miR-138 expression is downregulated in ovarian cancer tissues and miR-138 acts as a tumor suppressor gene by inhibiting SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑138 inhibits SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells

Zhu

Jin

2018

Exp Ther Med

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“…These two types of glioblastoma CSCs although possess distinct features of growth and differentiation, both of them were able to induce tumor formation at a comparable level in nude mice (Beier et al, 2007). Between these two types, SOX2 was the most up-regulated stemness gene in the CD133 + glioblastoma cells and controlled tumorigenesis of this disease (Song et al, 2016). Knockdown of SOX2 hindered CD133 + -mediated tumor formation abilities in vivo.…”

Section: Cd133 In Cancer Initiationmentioning

confidence: 99%

CD133 as a regulator of cancer metastasis through the cancer stem cells

Liou

2019

The International Journal of Biochemistry & Cell Biology

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Cancer stem cells are the cancer cells that have abilities to self-renew, differentiate into defined progenies, and initiate and maintain tumor growth. They also contribute to cancer metastasis and therapeutic resistance, both of which are the major causes of cancer mortality. Among the reported makers of the cancer stem cells, CD133 is the most well-known marker for isolating and studying cancer stem cells in different types of cancer. The CD133high population of cancer cells are not only capable of self-renewal, proliferation, but also highly metastatic and resistant to therapy. Despite very limited information on physiological functions of CD133, many ongoing studies are aimed to reveal the mechanisms that CD133 utilizes to modulate cancer dissemination and drug resistance with a long-term goal for bringing down the number of cancer deaths. In this review, in addition to the regulation of CD133, and its involvement in cancer initiation, and development, the recent updates on how CD133 modulates cancer dissemination, and therapeutic resistance are provided. The key signaling pathways that are upstream or downstream of CD133 during these processes are summarized. A comprehensive understanding of CD133-mediated cancer initiation, development, and dissemination through its pivotal role in cancer stem cells will offer new strategies in cancer therapy.

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“…More and more scholars have accepted the theory that tumors originate from CSCs. In addition to the above characteristics, CSCs also express several relatively specific biomarkers, such as CD133 [5], CD44 [6], NaNOG [7], and SOX2 [8], and overexpress anti-apoptotic genes, oncogenes, and other malignant biological markers, including telomerase and its hTERT subunit [9], BcL-2 [10], and survivin [11]. CSCs, tumor-like stem cells, or side population cells have been isolated from a variety of malignant tumors, including NPC [12,13].…”

Section: Introductionmentioning

confidence: 99%

The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways

Shen

Chen

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cancer stem cells (CSCs) are important factors for the continuous growth, recurrence, and metastasis of malignant tumors. They are responsible for the ineffectiveness of traditional radiotherapy and chemotherapy toward malignant tumors. Currently, stem cells or side-population cells have been isolated from many cancer cell lines and malignant tumor tissues, including nasopharyngeal carcinoma. Exploring the biological characteristics of CSCs for CSC-targeted therapy has gained importance. CSCs possess higher telomerase activity; thus, the use of the gene encoding telomerase inhibitor PinX1 gene to target telomerase in CSCs and inhibit proliferation, invasion, and metastasis of CSCs has become an important means for the treatment of malignant tumors. PinX1 may regulate complex pathways, including TRF1, Mad1/c-Myc, and p53. Methods: In this study, nasopharyngeal CD133+ CSCs were sorted using CD133 immunomagnetic beads by flow cytometry The successful isolation of CD133+ CSCs was confirmed by examining their surface markers, namely CD44, NaNOG, and SOX2 as well as their ability to undergo in vivo tumorigenesis and in vitro sphere formation, proliferation, migration, and invasion. In addition, CD133+ CSCs were transfected with the constructed PinX1 overexpression plasmid or siRNA and the resulting effects on their proliferation, migration, invasion, and apoptosis were detected using cell counting kit-8 (CCK-8), transwell assay, and scratch test, respectively. Furthermore, their effects on mRNA and protein levels of TRF1, TRF2, Mad1, c-Myc, and p53 were examined using quantitative real-time PCR and western blot, respectively. Results: The overexpression of PinX1 in CD133⁺ CSCs significantly decreased hTERT (P < 0.001), inhibited proliferation, migration, and invasion, induced apoptosis, and significantly decreased c-Myc mRNA levels (P < 0.001), while it increased TRF1, Mad1, and p53 mRNA levels (all P < 0.001). On the other hand, PinX1 silencing in CD133⁺ CSCs significantly decreased TRF1, Mad1, and p53 mRNA levels (all P < 0.01), while it increased hTERT and c-Myc mRNA levels (all P < 0.05). Conclusion: These results indicate that PinX1 downregulates telomerase activity in CD133⁺ CSCs, inhibits its proliferation, migration, and invasion, and induces apoptosis possibly through TRF1, Mad1/c-Myc, and p53–mediated pathways.

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Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem cells

Cited by 88 publications

References 38 publications

MicroRNA‑138 inhibits SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells

MicroRNA‑138 inhibits SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells

CD133 as a regulator of cancer metastasis through the cancer stem cells

The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways

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