Transcriptional Expression Analysis of Survivin Splice Variants Reveals Differential Expression of Survivin-3α in Breast Cancer

Abstract

Survivin, which is a novel member of the inhibitor of apoptosis family proteins, is known to play an important role in the regulation of cell cycle and apoptosis. Differential expression of survivin in tumor tissues introduces it as a new candidate molecular marker for cancer. Here we investigated the expression of survivin and its splice variants in breast tumors, as well as normal adjacent tissues obtained from the same patients. Thirty five tumors and 17 normal adjacent tissues from women diagnosed with breast cancer were explored in this study. Differential expression of different survivin splice variants was detected and semiquantitatively analyzed using reverse transcription-polymerase chain reaction. Results showed that survivin and its splice variants were differentially expressed in tumor specimens compared with normal adjacent tissues. The expression of survivin-3B and survivin-3α was specifically detected in tumor tissues compared with normal adjacent ones (53% in tumor tissues compared to 5% in normal adjacent for survivin-3B and 65% in tumor tissues and 0.0% in normal adjacent tissues for survivin-3α). Statistical analysis showed that survivin and survivin-ΔEx3 were upregulated in benign (90%, p<0.034) and malignant (76%, p<0.042) tumors, respectively. On the other hand, our results showed that survivin-2α (100% of the cases) was the dominant expressed variant of survivin in breast cancer. The data presented here showed that survivin splice variants were differentially expressed in benign and malignant breast cancer tissues, suggesting their potential role in breast cancer development. Differential expression of survivin-2α and survivin-3α splice variants highlights their usefulness as new candidate markers for breast cancer diagnosis and prognosis.

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis

“…In addition to the survivin-WT transcript, several transcript variants, generated by alternative splicing of the human survivin gene (BIRC5), have been identified: survivin-ΔΕx3 (a splice variant lacking exon 3), -2B (one variant retaining a part of intron 2 as a cryptic exon), and-3B (a novel exon 3B derived from a portion of www.nature.com/scientificreports/ intron 3) are currently well studied 40 , whereas other isoforms are not yet satisfactorily characterized 41 . Mokuda et al have already investigated the expression and function of survivin in different autoimmune diseases, and they have also identified elevated protein expression levels of survivin splice variants in rheumatoid arthritis tissues, confirmed by specific antibodies against survivin's different splice variants 42,43 .…”

Splicing imbalances in basal-like breast cancer underpin perturbation of cell surface and oncogenic pathways and are associated with patients’ survival

“…Examples are FANCD2, RAD54, BIRC5 (survivin) and ASF1B2021222324252627. Others amongst our list were detected to be differentially spliced in other forms of cancer, or cancer cell lines: FoxM1 CDKN3, ZBTB16, AURKB, CHEK1, SGOL1, SULF1, CDC45 and UBE2C282930313233343536373839.…”

Clinico-pathologic relevance of Survivin splice variant expression in cancer

“…Analysis of 73 brain neoplasms containing diffusely infiltrating astrocytoma failed to detect expression of the 3α variant[2]. Most recently, an intriguing study found expression of the survivin 3α to be specifically detected in breast tumor samples, while none was found in matching adjacent normal breast tissues[45], suggesting a potential role for this variant in breast cancer development.…”