Pancreatic cancer (PC) is one of the most common malignant cancers, ranking the seventh highest causes of cancer-related deaths globally. Recently, RNA N6-methyladenosine (m6A) is emerging as one of the most abundant RNA modifications in eukaryote cells, involved in multiple RNA processes including RNA translocation, alternative splicing, maturation, stability, and degradation. As reported, m6A was dynamically and reversibly regulated by its “writers”, “erasers”, and “readers”, Increasing evidence has revealed the vital role of m6A modification in the development of multiple types of cancers including PC. Currently, aberrant m6A modification level has been found in both PC tissues and cell lines. Moreover, abnormal expressions of m6A regulators and m6A-modified genes have been reported to contribute to the malignant development of PC. Here in this review, we will focus on the function and molecular mechanism of m6A-modulated RNAs including coding RNAs as well as non-coding RNAs. Then the m6A regulators will be summarized to reveal their potential applications in the clinical diagnosis, prognosis, and therapeutics of PC.
BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor associated with a poor prognosis. Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) has been reported to promote diverse tumors, but little is known about its role in HCC.MethodsExpression levels of UCHL3 in Huh7 and Hep3B cells were measured by qRT-PCR. UCHL3, Vimentin protein levels, and ubiquitination levels were determined by Western blot assay. co-immunoprecipitation, Immunofluorescence, and IHC were used to detect the interaction and expression association between UCHL3 and Vimentin in the cells. Wound healing and Transwell assays were used to measure cell migration. Spheroid formation assay were used to assess stem-like properties.ResultsUCHL3 expression was found to be significantly elevated in HCC and associated with poor prognosis. UCHL3 promoted migration and stem-like properties of HCC cells. Vimentin was identified as a potential de-ubiquitination substrate of UCHL3 and UCHL3 interacted with and promoted the de-ubiquitination of Vimentin, enhancing its stability. Moreover, the suppression of UCHL3 by siRNA or the inhibition by TCID upregulated ubiquitinated Vimentin. Vimentin attenuated the suppression of cell migration caused by knockdown of UCHL3.ConclusionUCHL3 was highly expressed in HCC and functioned as an oncogene. Vimentin is a novel substrate of UCHL3 and its stabilization and de-ubiquitination enhanced HCC cell migration.
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