A novel circular RNA hsa_circ_0060927 may serve as a potential diagnostic biomarker for human colorectal cancer

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ORIGINAL ARTICLE

A novel circular RNA hsa_circ_0060927 may serve as a potential diagnostic biomarker for human colorectal cancer Hossein Sadeghi1   · Mohammad Heiat1 Received: 26 April 2020 / Accepted: 2 August 2020 © Springer Nature B.V. 2020

Abstract CYP24A1 plays a role in strictly regulated vitamin D metabolism pathway and has been nominated as a prognostic biomarker for colorectal cancer (CRC). Increasing evidence suggests that circular RNAs (circRNAs) are involved in cancer initiation and progression; however, their diagnostic values in cancers as the new potential biomarkers are still not fully understood. In the present study, by using quantitative real-time polymerase chain reaction (qRT-PCR), we demonstrated that CYP24A1 and hsa_circ_0060927 were only transcribed in 33 and 25 out of 83 CRC tissues, respectively. In these samples, we demonstrated that CYP24A1 was up-regulated in both linear and circular forms (P 60  ≤60 Gender  Male  Female Clinical stage  I & II  III & IV

No. of patients (%)

Mean ± SD

P value

13 (0.52) 12 (0.48)

12.81 ± 4.49 12.93 ± 3.65

0.94

12 (0.48) 13 (0.52)

14.32 ± 3.73 11.68 ± 4.16

0.04

21 (0.84) 4 (0.16)

10.99 ± 3.47 9.11 ± 4.21

0.42

have hypothesized that the CYP24A1 might be a novel potential biomarker for the progression and prognosis of CRC [7]. Horváth et al. by analyzing the CYP24A1 expression at the mRNA and protein levels have shown that the

candidate oncogene CYP24A1 is a potential biomarker for CRC. They also have shown that CYP24A1 is up-regulated in the majority of the adenocarcinomas, but not in the normal and benign colonic tissues [21]. The co-expression of CYP24A1 and hsa_circ_0060927 has given us the idea that these transcripts are under common regulation. So, we investigated the existence of hsa_circ_0060927 in human HT-29 and HCT-116 colon cancer cell lines before and after treatment with the vitamin D. The HCT-116 and HT-29 colon cancer cell lines did not show expression of CYP24A1 and hsa_circ_0060927, but after vitamin D treatment the CYP24A1 and hsa_circ_0060927 were expressed. According to Lemay et al. the CYP24A1 gene is the most responsive primary vitamin D target gene [22]. Our results also confirmed the role of vitamin D as a key contributor of the transcription for both hsa_circ_0060927 and CYP24A1. The hsa_circ_0060927 mechanism of function has not been studied, but as mentioned, circRNAs act as microRNA (miRNA) sponges, thus could be part of the competing endogenous RNA network. For instance, circ_001569 acts as a miRNA sponge to bind and inhibit miR-145 activity in CRC cells and circHIPK3 sponges the miR-7 and promotes colorectal cancer growth and metastasis [10, 23]. A recent study predicted that hsa_ circ_0060927 targets the hsa-miR-224-3p, hsa-miR-29b1-5p, hsa-miR-522-3p, hsa-miR-661 and hsa-miR-1264 [15]. Considering this study, we predicted the miRNAs that target both hsa_circ_0060927 and CYP24A1 by TargetScan to specify the common miRNAs. The results showed mechanically, circ_0060927 acts as a miRNA sponge to directly inhibit hs