Figure 3.

Regulatory function of lncRNAs in BC resistance to anti-HER2 targeted therapy. Under trastuzumab exposure, TINCR is upregulated by H3K27 acetylation and induces trastuzumab resistance through sponging miR-125b and releasing HER2 in BC cells. Moreover, AFAP1-AS1 can be upregulated through H3K27 acetylation at its promoter region and guides AUF1 to bind to HER2 mRNA, leading to enhanced translation of HER2. AGAP2-AS1 increases H3K27 acetylation at the promoter region of MyD88, resulting in the activation of NF-κB signaling pathway and therapeutic resistance to trastuzumab. Moreover, another lncRNA, known as SNHG14, could inhibit trastuzumab-induced apoptosis through upregulating Bcl2. Intriguingly, several lncRNAs have been reported to confer trastuzumab resistance in surrounding cells through being engulfed in exosomes and incorporated by neighbor cells.