miR-155 increases stemness and decitabine resistance in triple-negative breast cancer cells by inhibiting TSPAN5.

Effective therapeutic targets for triple-negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration-approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR-155 is upregulated in BC, but whether and how miR-155 regulates DCA resistance is unclear. In this study, we demonstrated that miR-155 was upregulated in CD24- CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR-155 increased the number of CD24- CD44+ CSCs, DCA resistance and tumor clone formation in MDA-231 and BT-549 BC cells, and knockdown of miR-155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR-155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin-5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR-155 in promoting stemness and DCA resistance in BC cells. Our data show that miR-155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR-155/TSPAN5 signaling axis in the treatment of TNBC.

Mitochondrial genome of Cordyceps blackwelliae: organization, transcription, and evolutionary insights into Cordyceps.

Cordyceps is a diverse genus of insect pathogenic fungi, with about 180 accepted species, including some well-known ones used as ethnic medicine and/or functional food. Nevertheless, mitogenomes are only available for four members of the genus. The current study reports the mitogenome of Cordyceps blackwelliae, a newly described entomopathogenic fungus. The 42,257-bp mitogenome of the fungus encoded genes typically found in fungal mitogenomes, and a total of 14 introns inserted into seven genes, including cob (1 intron), cox1 (4), cox3 (3), nad1 (1), nad4 (1), nad5 (1), and rnl (3). RNA-Seq analysis revealed differential expression of mitochondrial genes and supported annotations resulting from in silico analysis. There was clear evidence for polycistronic transcription and alternative splicing of mitochondrial genes. Comparison among mitogenomes of five different Cordyceps species (i.e., C. blackwelliae, C. chanhua, C. militaris, C. pruinosa, and C. tenuipes) revealed a high synteny, with mitogenome size expansion correlating with intron insertions. Different mitochondrial protein-coding genes showed variable degrees of genetic differentiation among these species, but they were all under purifying selection. Mitochondrial phylogeny based on either nucleotide or amino acid sequences confirmed the taxonomic position of C. blackwelliae in Cordycipitaceae, clustering together with C. chanhua. This study promotes our understanding of fungal evolution in Cordyceps.