Abstract
Pin2/TRF1-interacting telomere inhibitor 1 (PinX1) was originally identified as a telomerase inhibitor, involved in maintaining telomerase activity, telomere length, and chromosomal stability. However, research has shown that PinX1 can have opposing molecular status in its expression patterns in several other tumor types. We thus investigated the genetic profile and biological implication of PinX1 in several human cancers using the cBioportal database. Our results showed that PinX1 deletion accounted for the most alterations, with the frequency of its deletion regularly occurring in pathological types of carcinosarcoma and adenocarcinoma. We found few instances of PinX1 gene mutations and 3D structural analysis demonstrated that these mutation sites were always located within telomerase inhibitor domains. Furthermore, our analysis of several human cancers from the cBioportal database revealed more frequent PinX1 homozygous depletion and PinX1 heterozygous deficiency, but both more infrequent PinX1 gain and rare instances of PinX1 amplification. The status of PinX1 genetic alterations was correlated with prognosis and may be tumor-type specific. As such, its biological function in tumorigenesis and later prognosis is complicated and may involve co-worked with NEIL2, R3HCC1, POLR3D, GTF2E2, and INTS10. In addition, we observed that PinX1 interacts with TERT, DKC1, PTGES3, and HSP90AA1. PinX1 mRNA expression was decreased in most selected cancer tissues, which could promote tumor growth and enhance tumorigenicity. Collectively, our data reveal PinX1 expression patterns and potential mechanisms in various human cancers. Further work will be needed to comprehensively examine its role in tumor genesis and progression.
Highlights
Telomeres cap the ends of chromosomes and are critical for maintaining genomic integrity
Our results showed that PinX1 deletion accounted for the most alterations, with the frequency of its deletion regularly occurring in pathological types of carcinosarcoma and adenocarcinoma
Previous work has shown that the telomeraseinhibitory domain of PinX1-C can block telomerase activity, shorten telomeres, induce cellular dysfunction, and suppress tumor growth [16]
Summary
Telomeres cap the ends of chromosomes and are critical for maintaining genomic integrity. Telomerase is the natural enzyme complex that elongates telomeres, doing so through the addition of telomere repeats at chromosomal ends. It plays a crucial role in maintaining telomere length, which has been implicated www.impactjournals.com/oncotarget in human cancer tumorigenesis through the maintenance of genomic stability and avoidance of senescence [2, 3]. Telomerase activity is responsible for the hallmark phenotype of human tumors—immortalization [4]. It has been detected in approximately 80% of human tumors and identified as a key step in human cellular tumorigenesis [5]. Communication with the shelterin complex is an essential step for telomerase to carry out its functions in telomere maintenance
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