Long noncoding RNA LINC00460 promotes the progression of cervical cancer via regulation of the miR-361-3p/Gli1 axis
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RESEARCH ARTICLE
Long noncoding RNA LINC00460 promotes the progression of cervical cancer via regulation of the miR‑361‑3p/Gli1 axis Fan Li1,2 · Weipei Zhu1 · Zhijie Wang2 Received: 8 July 2020 / Accepted: 2 October 2020 © Japan Human Cell Society 2020
Abstract Mounting evidence indicates that the long non-coding RNA (lncRNA) LINC00460 plays an oncogenic role in tumor progression; however, the role of LINC00460 in cervical cancer (CC) remains unknown. In this study, we found that LINC00460 was frequently upregulated in CC tissues and cell lines. Knockdown of LINC00460 repressed CC cell growth and invasion in vitro and attenuated tumorigenesis in vivo. Mechanistically, miR-361-3p was predicted as a direct target of LINC00460 by bioinformatics analysis, which was further confirmed by qRT-PCR, dual-luciferase reporter assays, and rescue experiments. Furthermore, miR-361-3p targeted the 3′ untranslated region (UTR) of Gli1 mRNA and repressed its expression. Taken together, our study revealed that LINC00460 functions as an oncogenic lncRNA in CC, indicating the likely participation of the LINC00460/miR-361-3p/Gli1 pathway in the disease. Accordingly, our results provide new insight into CC tumorigenesis. Keywords Cervical cancer · LINC00460 · miR-361-3p · Gli1 · Cell invasion
Introduction Cervical cancer (CC) is one of the most common malignancies in women globally and a prominent cause of death in women in many developing nations [1]. Although standard vaccination against human papillomavirus, rapid surgical treatment, and periodic cancer screening have resulted in a substantial decline in the prevalence of CC, it remains among the most prolific lethal diseases in women. Therefore, it is critical to elucidate the mechanisms underlying the disease and determine novel biomarkers for the prevention and treatment of CC. Modern integrative genomic research has shown that the vast majority of human genome transcripts are non-coding * Weipei Zhu [email protected] * Zhijie Wang [email protected] 1
Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Gusu District, Suzhou 215000, China
Department of Gynaecology and Obestetrics, Shanghai the Eighth People’s Hospital, No.8 Caobao Road, Xuhui District, Shanghai 200235, China
2
RNAs with no protein-coding capacity [2]. Long non-coding RNAs (lncRNAs), which are greater than 200 nt in length, are recently discovered vital members of the non-coding RNA family [3]. lncRNAs can function as competing endogenous RNAs (ceRNAs) and sponge microRNAs (miRNAs), thereby derepressing compound target genes. Mounting evidence indicates that aberrant lncRNA expression is involved in different human diseases, particularly cancers [4]. To date, many human lncRNAs have been shown to be dysregulated in CC, such as LINC00473, LNMICC, XLOC_006390, and SNHG12 [5–8], which contribute to the development and progression of CC. In particular, LINC00460, a newly identified lncRNA encoded on chromosome 13q33.2, has recently been descr
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