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Open AccessArticle

How Does a Tumor Get Its Shape? MicroRNAs Act as Morphogens at the Cancer Invasion Front

1
“Carol Davila” University of Medicine and Pharmacy, RO-020021 Bucharest, Romania
2
Department of Surgery, Fundeni Clinical Hospital, RO-022328 Bucharest, Romania
3
Polytechnic University of Bucharest, RO-060042 Bucharest, Romania
4
Department of Family and Community Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
5
Guy’s and St. Thomas’ NHS Foundation Trust, London SE1 7EH, UK
6
Translational Molecular Pathology Department, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
7
Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Non-Coding RNA 2020, 6(2), 23; https://doi.org/10.3390/ncrna6020023
Received: 20 May 2020 / Revised: 6 June 2020 / Accepted: 7 June 2020 / Published: 10 June 2020
(This article belongs to the Special Issue Clinical Potential of Non-coding RNAs in Cancer)
The generation and organization of the invasion front shape of neoplasms is an intriguing problem. The intimate mechanism is not yet understood, but the prevailing theory is that it represents an example of morphogenesis. Morphogenesis requires the presence of specific molecules, known as morphogens (activators and inhibitors), which can diffuse and elicit dose-dependent responses in their target cells. Due to their ability to modulate most of the coding transcriptome, their well-established role in embryogenesis, and their capacity to rapidly move between neighboring and distant cells, we propose microRNAs as inhibitors that could shape the cancer invasion front. In order to explain the genesis of the tumor border, we use Alan Turing’s reaction diffusion model, refined by Meinhardt and Gierer. This assumes the existence of an activator called a, and an inhibitor called h, which we hypothesize could be a freely moving microRNA. We used the fractal dimension as a measure of tumor border irregularity. We observed that the change in fractal dimension associates with variations in the diffusion coefficient of the activator (Da) or the inhibitor (Dh). We determined that the fractal dimension remains constant (i.e., the irregularity of the tumor border does not change) across a Dh interval, which becomes narrower as Da rises. We therefore conclude that a change in fractal dimension occurs when the balance between Da and Dh is disrupted. Biologically, this could be explained by a faulty distribution of the inhibitor caused by an abnormal density of the intercellular connection network. From a translational perspective, if experimentally confirmed, our observations can be used for a better diagnosis of cancer aggressiveness. View Full-Text
Keywords: morphogenesis; invasion front; tumor border; microRNA; diffusion morphogenesis; invasion front; tumor border; microRNA; diffusion
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MDPI and ACS Style

Vasilescu, C.; Tanase, M.; Giza, D.; Procopiuc, L.; Dragomir, M.P.; Calin, G.A. How Does a Tumor Get Its Shape? MicroRNAs Act as Morphogens at the Cancer Invasion Front. Non-Coding RNA 2020, 6, 23.

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