Fig. 2
From: Cell-specific mechanisms of TMEM16A Ca2+-activated chloride channel in cancer
TMEM16A expression is upregulated via transcriptional regulation, epigenetic regulation and microRNAs in cancer. TMEM16A upregulation is induced by IL-4 and IL-13 [64, 65], which bind to their receptors and subsequently activate JAK/STAT6 signaling. STAT6 binds to the TMEM16A promoter and increases the transcription of the TMEM16A gene. Testosterone (T) induces TMEM16A upregulation by binding to the androgen receptor (AR), which subsequently increases the transcription of the TMEM16A gene [71]. Histone deacetylase (HDAC) inhibitors reduce TMEM16A expression in breast and prostate cell lines [77]. Promoter hypomethylation contributed to TMEM16A overexpression in HPV-negative HNSCC [75] and promoter hypermethylation results in decreased TMEM16A expression in metastatic lymph node tissues [74]. miR-132 and miR-381 binds to the 3′ UTR of TMEM16A mRNA, resulting in TMEM16A downregulation [49, 55]. Downregulation of miR-132 and miR-318 contributes to TMEM16A in patients with colorectal cancer [49] and gastric cancer [55]