Researchers identified a series of hub long noncoding RNAs in gastrointestinal stromal tumors (GISTs). This finding sheds light on the malignant transformation of these types of tumors.

“This work presents valuable information about the malignant transformation of GISTs and provides numerous candidate prognostic biomarkers and therapeutic targets,” the researchers wrote in the study, published in the journal Cell Death and Disease.

The molecular mechanisms involved in the malignant character of GISTs are not well understood. The identification of new biomarkers of malignancy can help better predict the prognosis of GISTs. And a better understanding of the molecular mechanisms involved in the malignant transformation of GISTs can help identify novel therapeutic targets for the disease.

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. Most (66%) occur in the stomach and gastric GISTs have a lower malignant potential than tumors found elsewhere in the GI tract. Micrograph of gastrointestinal stromal tumor of the stomach.
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In the present study, a team led by Bo Zhang, MD, from Sichuan University, China investigated the expression profiles of long noncoding RNAs and mRNAs that may be associated with the malignant transformation of GISTs. 

Long noncoding RNAs are involved in different biological processes such as regulation of gene expression, translation, nuclear organization, and epigenetic modification. Recent studies have shown that they may also be involved in the development of cancer by regulating processes such as cell proliferation, apoptosis, invasion, and migration.

The researchers conducted RNA-sequencing analysis of low-risk and high-risk GISTs classified as such based on tumor size and mitotic rate. They then selected candidate hub long noncoding RNAs using Oncomine analysis. 

In this way, they identified a series of key pathways and hub long noncoding RNAs that play a role in the malignant transformation of GISTs.

They then further analyzed the expression and correlation with prognosis of the long noncoding RNA DNM3OS. They found a tight association between clinical signatures of the disease and DNM3OS. Specifically, DNM3OS was upregulated in GISTs classed as high risk based on tumor size as well as mitotic rate, and this correlated with a worse prognosis.

Moreover, the team also found that DNM3OS regulated the expression of the cancer oncogenes GLUT4 and CD36, thereby promoting GIST cell proliferation and mitosis.

“Collectively, these results improve our understanding of the malignant transformation of GISTs and unveil a series of hub lncRNAs in GISTs,” the authors concluded.

Reference

Yin X, Yin Y, Dai L, et al. Integrated analysis of long non-coding RNAs and mRNAs associated with malignant transformation of gastrointestinal stromal tumors. Cell Death Dis. 2021;12,669. doi:10.1038/s41419-021-03942-y

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