The Intermediate Filament Vimentin Mediates MicroRNA miR-378 Function in Cellular Self-renewal by Regulating the Expression of the Sox2 Transcription Factor

Deng, Zhaoqun; Du, William W.; Fang, Ling; Shan, Sze Wan; Qian, Jun; Jiang, Lin; Qian, Wei; Ma, Ji‐chun; Rutnam, Zina Jeyapalan; Yang, Burton B.

doi:10.1074/jbc.m112.418830

Cited by 44 publications

(30 citation statements)

References 52 publications

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“…A similar phenotype was also observed when miR-378 was overexpressed in chronic myeloid leukemia K562 cells [23]. The over-expression of miR-378 in a human primary glioblastoma cell line promoted a stem cell phenotype with an increase in proliferation, adipogeneic differentiation, and colony formation [24]. These observations align with the loss in proliferation potential (see Supplemental Table S2) and corresponding loss in miR-378 expression that we observe as ASC are cultured over time.…”

Section: Discussionsupporting

confidence: 84%

microRNAs in Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Undergo Rapid Culture-Induced Changes in Expression, Including miR-378 which Promotes Adipogenesis

Iminitoff

Damani

Williams

et al. 2020

IJMS

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There is clinical interest in using human adipose tissue-derived mesenchymal stromal cells (ASC) to treat a range of inflammatory and regenerative conditions. Aspects of ASC biology, including their regenerative potential and paracrine effect, are likely to be modulated, in part, by microRNAs, small RNA molecules that are embedded as regulators of gene-expression in most biological pathways. However, the effect of standard isolation and expansion protocols on microRNA expression in ASC is not well explored. Here, by using an untouched and enriched population of primary human ASC, we demonstrate that there are rapid and significant changes in microRNA expression when ASC are subjected to standard isolation and expansion methods. Functional studies focusing on miR-378 indicate that these changes in expression may have an impact on phenotype and function. Specifically, we found that increased levels of miR-378 significantly promoted adipogenesis in late passage ASC. These results are informative to maximizing the potential of ASC for use in various clinical applications, and they have implications for targeting microRNAs as a therapeutic strategy for obesity or metabolic disease.

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Section: Discussionsupporting

confidence: 84%

microRNAs in Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Undergo Rapid Culture-Induced Changes in Expression, Including miR-378 which Promotes Adipogenesis

Iminitoff

Damani

Williams

et al. 2020

IJMS

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“…miR-378 is involved in promoting cell survival, tumor growth, and angiogenesis in glioblastoma cells [26], in regulating osteoblast differentiation [28] and in tumor cell self-renewal and chemoresistance [27]. However, the function of miR-378 in liver cancer cells has not been reported thus far.…”

Section: Discussionmentioning

confidence: 99%

“…Our study demonstrated that miR-378 enhanced liver cancer cell proliferation, migration, invasion and metastasis. In addition to these functions, miR-378 also participates in cellular self-renewal [27] and osteoblast differentiation regulation [28]. Thus, considering its biological characteristics, miR-378 is categorized as an oncogene.…”

Section: Discussionmentioning

confidence: 99%

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MiR-378 Promotes the Migration of Liver Cancer Cells by Down-Regulating Fus Expression

Jiang

Qian

et al. 2014

Cell Physiol Biochem

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Background: miR-378 regulates osteoblast differentiation and participates in tumor cell self-renewal and chemo-resistance. However, the function of miR-378 in liver cancer cell migration has not been reported to date. Methods: miR-378 expression was examined using real-time quantitative PCR. HepG2 cell migration and liver cell invasion were examined using wound-healing and cell invasion assays. Additionally, HepG2 cell metastasis was analyzed in nude mice. Results: miR-378 over-expression enhances HepG2 cell proliferation, migration and liver cell invasion. Typical metastatic lesions were found in the livers of mice injected with miR-378-transfected cells, and high levels of the CMV promoter were detected in the nodules, indicating that miR-378 promoted the metastasis of the tumor cells to the liver. We also demonstrated that miR-378 down-regulated Fus expression. Conclusions: Our results suggested that miR-378 enhanced cell migration and metastasis by down-regulating Fus expression.

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“…With one notable exception, SOX2-targeting miRs are associated with downregulation of SOX2. However, Deng et al reported that miR-378 increases SOX2 expression in breast cancer [ 154 ]. Although the types of breast cancer specimens examined were not described, they noted miR-378 was expressed at higher levels in breast tumor tissue than adjacent non-tumorigenic tissue.…”

Section: Regulation Of Sox2 Expressionmentioning

confidence: 99%

The dark side of SOX2: cancer - a comprehensive overview

Wuebben

Rizzino²

2017

Oncotarget

182

161

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The pluripotency-associated transcription factor SOX2 is essential during mammalian embryogenesis and later in life, but SOX2 expression can also be highly detrimental. Over the past 10 years, SOX2 has been shown to be expressed in at least 25 different cancers. This review provides a comprehensive overview of the roles of SOX2 in cancer and focuses on two broad topics. The first delves into the expression and function of SOX2 in cancer focusing on the connection between SOX2 levels and tumor grade as well as patient survival. As part of this discussion, we address the developing connection between SOX2 expression and tumor drug resistance. We also call attention to an under-appreciated property of SOX2, its levels in actively proliferating tumor cells appear to be optimized to maximize tumor growth - too little or too much SOX2 dramatically alters tumor growth. The second topic of this review focuses on the exquisite array of molecular mechanisms that control the expression and transcriptional activity of SOX2. In addition to its complex regulation at the transcriptional level, SOX2 expression and activity are controlled carefully by microRNAs, long non-coding RNAs, and post-translational modifications. In the Conclusion and Future Perspectives section, we point out that there are still important unanswered questions. Addressing these questions is expected to lead to new insights into the functions of SOX2 in cancer, which will help design novels strategies for more effectively treating some of the most deadly cancers.

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The Intermediate Filament Vimentin Mediates MicroRNA miR-378 Function in Cellular Self-renewal by Regulating the Expression of the Sox2 Transcription Factor

Cited by 44 publications

References 52 publications

microRNAs in Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Undergo Rapid Culture-Induced Changes in Expression, Including miR-378 which Promotes Adipogenesis

microRNAs in Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Undergo Rapid Culture-Induced Changes in Expression, Including miR-378 which Promotes Adipogenesis

MiR-378 Promotes the Migration of Liver Cancer Cells by Down-Regulating Fus Expression

The dark side of SOX2: cancer - a comprehensive overview

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