Drosha-independent miR-6778-5p strengthens gastric cancer stem cell stemness via regulation of cytosolic one-carbon folate metabolism.

Cancer Letters
Maojia ZhaoManran Liu

Abstract

Drosha-dependent canonical microRNAs (miRNAs) play a crucial role in the biological functions and development of cancer. However, the effects of Drosha-independent non-canonical miRNAs remain poorly understood. In our previous work, we found a set of aberrant miRNAs, including some upregulated miRNAs, called Drosha-independent noncanonical miRNAs, in Drosha-knockdown gastric cancer (GC) cells. Surprisingly, Drosha-silenced GC cells still retained strong malignant properties (e.g., proliferation ability and cancer stem cell (CSC) characteristics), indicating that aberrantly upregulated non-canonical miRNAs may play an important role in the maintenance of the malignant properties in GC cells that express low Drosha levels. Here, we report that miR-6778-5p, a noncanonical miRNA, acts as a crucial regulator for maintenance of CSC stemness in Drosha-silenced GC cells. MiR-6778-5p belongs to the 5'-tail mirtron type of non-canonical miRNAs and is transcript splice-derived from intron 5 of SHMT1 (coding cytoplasmic serine hydroxymethyltransferase). It positively regulates expression of its host gene, SHMT1, via targeting YWHAE in Drosha-knockdown GC cells. Similar to its family member SHMT2, SHMT1 plays a crucial role in folate-depend...Continue Reading

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Citations

Jul 11, 2020·Chinese Medical Journal·Si-Ran WuYong-Quan Shi
Dec 18, 2020·Frontiers in Oncology·Tiziana AnneseDomenico Ribatti
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Nan JingYu-Xiang Fang
Jun 15, 2021·Journal of Cellular and Molecular Medicine·Yangfeng ShiKejing Ying
Jun 23, 2021·Wiley Interdisciplinary Reviews. RNA·Uzma SalimPerumal Vivekanandan
Jul 13, 2021·Frontiers in Oncology·Martina AddeoPellegrino Mazzone

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