Human Endogenous Retrovirus-H-Derived miR-4454 Inhibits the Expression of DNAJB4 and SASH1 in Non-Muscle-Invasive Bladder Cancer

Author:

Park Eun Gyung12ORCID,Lee Du Hyeong12,Kim Woo Ryung12,Lee Yun Ju12,Bae Woo Hyeon12,Kim Jung-min12,Shin Hae Jin12,Ha Hongseok3,Yi Joo Mi4,Cho Ssang Goo5ORCID,Choi Yung Hyun6ORCID,Leem Sun Hee7,Cha Hee Jae8ORCID,Kim Sang Woo9,Kim Heui Soo29

Affiliation:

1. Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Republic of Korea

2. Institute of Systems Biology, Pusan National University, Busan 46241, Republic of Korea

3. Division of Life Sciences, Korea University, Seoul 02841, Republic of Korea

4. Department of Microbiology and Immunology, Inje University College of Medicine, Busan 47392, Republic of Korea

5. Department of Stem Cell & Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University, Seoul 05029, Republic of Korea

6. Department of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, Republic of Korea

7. Department of Biological Science, Dong-A University, Busan 49315, Republic of Korea

8. Department of Parasitology and Genetics, College of Medicine, Kosin University, Busan 49104, Republic of Korea

9. Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea

Abstract

Although most human endogenous retroviruses (HERVs) have been silenced and lost their ability to translocate because of accumulated mutations during evolution, they still play important roles in human biology. Several studies have demonstrated that HERVs play pathological roles in numerous human diseases, especially cancer. A few studies have revealed that long non-coding RNAs that are transcribed from HERV sequences affect cancer progression. However, there is no study on microRNAs derived from HERVs related to cancer. In this study, we identified 29 microRNAs (miRNAs) derived from HERV sequences in the human genome. In particular, we discovered that miR-4454, which is HERV-H-derived miRNA, was upregulated in non-muscle-invasive bladder cancer (NMIBC) cells. To figure out the effects of upregulated miR-4454 in NMIBC, genes whose expression was downregulated in NMIBC, as well as tumor suppressor genes, were selected as putative target genes of miR-4454. The dual-luciferase assay was used to determine the negative relationship between miR-4454 and its target genes, DNAJB4 and SASH1, and they were confirmed to be promising target genes of miR-4454. Taken together, this study suggests that the upregulation of miR-4454 derived from HERV-H in NMIBC reduces the expression of the tumor suppressor genes, DNAJB4 and SASH1, to promote NMIBC progression.

Publisher

MDPI AG

Subject

Genetics (clinical),Genetics

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