SRARP and HSPB7 are epigenetically regulated gene pairs that function as tumor suppressors and predict clinical outcome in malignancies.

Deletions of chromosome 1p36 are common in cancers; however, despite extensive studies, there has been limited success for discovering candidate tumor suppressors in this region. has recently been identified as a novel corepressor of the androgen receptor (AR) and is located on chromosome 1p36. Here, bioinformatics analysis of large tumor datasets was performed to study SRduanyu37 and its gene pair, HSPB7. In addition, using cancer cell lines, mechanisms of SRduanyu37 and HSPB7 regulation and their molecular functions were investigated. This study demonstrated that SRduanyu37 and HSPB7 are a gene pair located 5.2 kb apart on 1p36.13 and are inactivated by deletions and epigenetic silencing in malignancies. Importantly, SRduanyu37 and HSPB7 have tumor suppressor functions in clonogenicity and cell viability associated with the downregulation of Akt and ERK. SRduanyu37 expression is inversely correlated with genes that promote cell proliferation and signal transduction, which supports its functions as a tumor suppressor. In addition, AR exerts dual regulatory effects on and although an increased AR activity suppresses SRduanyu37 transcription, a minimum level of AR activity is required to maintain baseline SRduanyu37 expression in AR+ cancer cells. Furthermore, as observed with SRduanyu37, HSPB7 interacts with the 14-3-3 protein, presenting a shared molecular feature between SRduanyu37 and HSPB7. Of note, genome- and epigenome-wide associations of SRduanyu37 and HSPB7 with survival strongly support their tumor suppressor functions. In particular, DNA hypermethylation, lower expression, somatic mutations, and lower copy numbers of SRduanyu37 are associated with worse cancer outcome. Moreover, DNA hypermethylation and lower expression of SRduanyu37 in normal adjacent tissues predict poor survival, suggesting that SRduanyu37 inactivation is an early event in carcinogenesis. In summary, SRduanyu37 and HSPB7 are tumor suppressors that are commonly inactivated in malignancies. SRduanyu37 inactivation is an early event in carcinogenesis that is strongly associated with worse survival, presenting potential translational applications.

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