Calcium- and voltage-activated potassium (BK) channel is an ubiquitously expressed membrane proteinwhich is involved in diverse cellular functions under both physiological and diseased (such as endocrinesystem diseases and cancers) states. It has now emerged as a potential biomarker during tumourdevelopment with recent evidence showing the channel’s involvement in promoting cancer cellproliferation, invasion and migration during carcinogenesis. The molecular mechanism underlying BKchannel’s role in cancer remains unclear. Aberrant alternative splicing of the BK channel pore-forminggene KCNMA1 has been implicated from our previous study on the regulation of the channel’s physiologicalfunctions. We have recently identified 20 novel alternative exons of KCNMA1 by interrogating through varioustranscriptomic (RNA-seq) data using a bioinformatics approach. These are in addition to the 32 knownexons of the gene. Expression of these alternative exons seems to be tissue specific. Furthermore, ouranalysis of breast cancer transcriptomes revealed two regions within KCNMA1 which are more susceptibleto active alternative splicing in breast cancer where 10 of the newly identified exons could also be foundto be expressed. Interestingly, differential expression of a plethora of alternatively spliced varianttranscripts is one of the most striking features in both triple positive and triple negative breast cancers.The transcriptional profile of KCNMA1  does not seem to be histophenotype specific. However, the overallexon transcriptional levels in triple-positive breast cancer tissues are higher than those in triple-negativebreast cancer tissues. A single cell/tissue is known to express multiple alternatively spliced variant transcripts of KCNMA1 andeach of such transcripts may also play diverse physiological functions in different cells/tissue, which addsto the complexity of tissue-specific transcriptional splicing process. We have observed this in ourpreliminary laboratory experiments whereby a single KCNMA1 variant exhibited different cellular functionalproperties in different breast cell lines. Overexpression of a variant known as ZERO in the MCF-7 triplepositive breast cell line promoted proliferation and inhibited the migration of the cells. On the other hand,the same alternatively spliced variant transcript was found to aid in faster cellular migration in the MDA-MB-231, a triple-negative breast cancer cell line. Our work so far has, therefore, added more weight to the potential of KCNMA1 serving as a biomarker forcancer development.B E Y O N D | O C T . T O D E C . 2 0 1 9 | I S S U E 1 9 | R E S E A R C H I S S U EI N V E S T I G A T I O N O F B K C H A N N E L A S AP O T E N T I A L P R O G N O S T I C B I O M A R K E R A N DT H E R A P E U T I C T A R G E T F O R B R E A S T C A N C E R 5D r . L i e C h e n , A s s o c i a t e P r o f e s s o rLeft: Tissue distribution tree of BK channel alpha-subunit splicing variantRight: Alternative splicing exons (PINK) of KCNMA1 in triple positive and triple negative breast cancer tissues
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