SOX9: Advances in Gynecological Malignancies

Transcription factors of the SOX family were first discovered in mammals in 1990. The sex-determining region Y box 9 belongs to the SOX transcription factor family. It plays an important role in inducing tissue and cell morphogenesis, survival, and many developmental processes. Furthermore, it has been shown to be an oncogene in many tumors. Gynecological malignancies are tumors that occur in the female reproductive system and seriously threaten the lives of patients. Common gynecological malignancies include ovarian cancer, cervical cancer, and endometrial cancer. So far, the molecular mechanisms related to the incidence and development of gynecological malignancies remain unclear. This makes it particularly important to discover their common causative molecule and thus provide an effective therapeutic target. In recent years, studies have found that multiple mechanisms are involved in regulating the expression of the sex-determining region Y box 9, leading to the occurrence and development of gynecological malignancies. In this review, we discuss the prognostic value of SOX9 expression and the potential of targeting SOX9 for gynecological malignancy treatment. We also discuss progress regarding the role of SOX9 in gynecological malignancy pathogenesis through its mediation of important mechanisms, including tumor initiation and proliferation, apoptosis, migration, invasion, chemoresistance, and stem cell maintenance.

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The role of autophagy in morphogenesis and stem cell maintenance

Histochemistry and Cell Biology ◽

10.1007/s00418-018-1751-0 ◽

2018 ◽

Vol 150 (6) ◽

pp. 721-732 ◽

Cited By ~ 5

Author(s):

Eric Bekoe Offei ◽

Xuesong Yang ◽

Beate Brand-Saberi

Keyword(s):

Stem Cell ◽

Stem Cell Maintenance ◽

Cell Maintenance

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The KDM4/JMJD2 histone demethylases are required for hematopoietic stem cell maintenance

Blood ◽

10.1182/blood.2019000855 ◽

2019 ◽

Vol 134 (14) ◽

pp. 1154-1158 ◽

Cited By ~ 13

Author(s):

Karl Agger ◽

Koutarou Nishimura ◽

Satoru Miyagi ◽

Jan-Erik Messling ◽

Kasper Dindler Rasmussen ◽

...

Keyword(s):

Myeloid Leukemia ◽

Clinical Use ◽

Histone Demethylases ◽

Hematopoietic Stem ◽

Stem Cell Maintenance ◽

Demethylase Activity ◽

Cell Maintenance ◽

Acute Myeloid

Abstract KDM4 and JMJD2 are histone demethylases that are considered promising targets for treatment of MLL translocation–bearing acute myeloid leukemia. Agger and colleagues demonstrate an important role of KDM4 activity in long-term normal hematopoiesis that should be considered when contemplating the clinical use of long-term inhibition of KDM4 demethylase activity.

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Integrated Transcriptome and Proteome Analyses Reveal the Regulatory Role of miR-146a in Human Limbal Epithelium via Notch Signaling

Cells ◽

10.3390/cells9102175 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2175

Author(s):

Adam J. Poe ◽

Mangesh Kulkarni ◽

Aleksandra Leszczynska ◽

Jie Tang ◽

Ruchi Shah ◽

...

Keyword(s):

Wound Healing ◽

Stem Cell ◽

Fine Tuning ◽

Regulatory Role ◽

Human Cornea ◽

Notch 1 ◽

Stem Cell Maintenance ◽

Limbal Epithelium ◽

Cell Maintenance

MiR-146a is upregulated in the stem cell-enriched limbal region vs. central human cornea and can mediate corneal epithelial wound healing. The aim of this study was to identify miR-146a targets in human primary limbal epithelial cells (LECs) using genomic and proteomic analyses. RNA-seq combined with quantitative proteomics based on multiplexed isobaric tandem mass tag labeling was performed in LECs transfected with miR-146a mimic vs. mimic control. Western blot and immunostaining were used to confirm the expression of some targeted genes/proteins. A total of 251 differentially expressed mRNAs and 163 proteins were identified. We found that miR-146a regulates the expression of multiple genes in different pathways, such as the Notch system. In LECs and organ-cultured corneas, miR-146a increased Notch-1 expression possibly by downregulating its inhibitor Numb, but decreased Notch-2. Integrated transcriptome and proteome analyses revealed the regulatory role of miR-146a in several other processes, including anchoring junctions, TNF-α, Hedgehog signaling, adherens junctions, TGF-β, mTORC2, and epidermal growth factor receptor (EGFR) signaling, which mediate wound healing, inflammation, and stem cell maintenance and differentiation. Our results provide insights into the regulatory network of miR-146a and its role in fine-tuning of Notch-1 and Notch-2 expressions in limbal epithelium, which could be a balancing factor in stem cell maintenance and differentiation.

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Insulin-independent role of adiponectin receptor signaling in Drosophila germline stem cell maintenance

Developmental Biology ◽

10.1016/j.ydbio.2014.12.033 ◽

2015 ◽

Vol 399 (2) ◽

pp. 226-236 ◽

Cited By ~ 14

Author(s):

Kaitlin M. Laws ◽

Leesa L. Sampson ◽

Daniela Drummond-Barbosa

Keyword(s):

Stem Cell ◽

Adiponectin Receptor ◽

Germline Stem Cell ◽

Receptor Signaling ◽

Stem Cell Maintenance ◽

Cell Maintenance

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The Importance of Ubiquitination and Deubiquitination in Cellular Reprogramming

Stem Cells International ◽

10.1155/2016/6705927 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 33

Author(s):

Bharathi Suresh ◽

Junwon Lee ◽

Kye-Seong Kim ◽

Suresh Ramakrishna

Keyword(s):

Stem Cell ◽

Transcription Factors ◽

Embryonic Stem ◽

Cellular Reprogramming ◽

Stem Cell Maintenance ◽

Opposite Action ◽

Induced Pluripotent ◽

Related Proteins ◽

Cell Maintenance

Ubiquitination of core stem cell transcription factors can directly affect stem cell maintenance and differentiation. Ubiquitination and deubiquitination must occur in a timely and well-coordinated manner to regulate the protein turnover of several stemness related proteins, resulting in optimal embryonic stem cell maintenance and differentiation. There are two switches: an E3 ubiquitin ligase enzyme that tags ubiquitin molecules to the target proteins for proteolysis and a second enzyme, the deubiquitinating enzyme (DUBs), that performs the opposite action, thereby preventing proteolysis. In order to maintain stemness and to allow for efficient differentiation, both ubiquitination and deubiquitination molecular switches must operate properly in a balanced manner. In this review, we have summarized the importance of the ubiquitination of core stem cell transcription factors, such as Oct3/4, c-Myc, Sox2, Klf4, Nanog, and LIN28, during cellular reprogramming. Furthermore, we emphasize the role of DUBs in regulating core stem cell transcriptional factors and their function in stem cell maintenance and differentiation. We also discuss the possibility of using DUBs, along with core transcription factors, to efficiently generate induced pluripotent stem cells. Our review provides a relatively new understanding regarding the importance of ubiquitination/deubiquitination of stem cell transcription factors for efficient cellular reprogramming.

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