Abstract
The roles of serine protease inhibitor Kazal type 1 (SPINK1) in multiple types of cancers have been significantly documented. However, its specific roles in hepatocellular carcinoma (HCC) remain to be investigated. This study found that SPINK1 is upregulated in HCC and its upregulation correlates with poor prognosis. Besides, functional assays revealed that SPINK1 promotes cell proliferation, cell cycle, and invasion in vitro. Through bioinformatics analysis, we speculate that circRPS16 regulates SPINK1 expression by sponging miR-876-5p. This was further verified by the dual-luciferase reporter and fluorescent in situ hybridization (FISH) assays. Subsequently, rescue assays verified that circRPS16 promotes cell proliferation, cell cycle, and invasion through miR-876-5p. Importantly, silencing circRPS16 inhibited tumor growth by downregulating SPINK1 expression in vivo. Collectively, our results confirm that SPINK1 is a downstream target of circRPS16. Besides, circRPS16 and SPINK1 are oncogenic factors in HCC progression; they provide novel diagnostic and therapeutic targets for HCC patients.
Highlights
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer that has emerged as a critical global medical problem
Based on the GSE14520 dataset, we found that the serine protease inhibitor Kazal type 1 (SPINK1) mRNA levels were significantly upregulated in tumor samples (Figure 1A)
By analyzing the Gene Expression Omnibus (GEO) database, we found that SPINK1 was upregulated in the HCC tissues; this was further verified using quantitative reverse transcription PCR (qRT-PCR) in 25 paired HCC tumors and adjacent nontumors
Summary
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer that has emerged as a critical global medical problem. Circular RNAs (circRNAs) are a novel class of noncoding RNAs that exert critical regulatory roles in physiological and pathological processes. Unlike the linear RNAs, circRNAs are characterized by covalently closed-loop structures formed through a specific back-splicing mechanism of 5′ and 3′end [3]. This specific structure enables circRNAs to tolerate RNase R digestion [4]. Based on the above characteristics, circRNAs may serve as potential diagnostic biomarkers and therapeutic molecules. Recent studies revealed the important roles of circRNAs in the progression of HCC. Functional exploration of circRNAs may provide a novel diagnostic and therapeutic strategy for HCC
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