title: MicroRNA-423-5p Promotes Autophagy in Cancer Cells and Is Increased in Serum From Hepatocarcinoma Patients Treated With Sorafenib.
abstract: Hepatocellular carcinoma (HCC) is the third cause of cancer-related deaths worldwide. Sorafenib is the only approved drug for patients with advanced HCC but has shown limited activity. microRNAs (miRs) have been involved in several neoplasms including HCC suggesting their use or targeting as good tools for HCC treatment. The purpose of this study was to identify novel approaches to sensitize HCC cells to sorafenib through miRs. miR-423-5p was validated as positive regulator of autophagy in HCC cell lines by transient transfection of miR and anti-miR molecules. miR-423-5p expression level was evaluated by real-time polymerase chain reaction (PCR) in sera collected from 39 HCC patients before and after treatment with sorafenib. HCC cells were cotreated with sorafenib and miR-423-5p and the effects on cell cycle, apoptosis, and autophagy were evaluated. Secretory miR-423-5p was upregulated both in vitro and in vivo by sorafenib treatment and its increase was correlated with response to therapy since 75% of patients in which an increase of secretory miR423-5p was found were in partial remission or stable disease after 6 moths from the beginning of therapy. HCC cells transfected with miR-423-5p showed an increase of cell percentage in S-phase of cell cycle paralleled by a similar increase of autophagic cells evaluated at both fluorescence activated cell sorter (FACS) and transmission electron microscopy. Our results suggest the miR423-5p can be used as a useful tool to predict response to sorafenib in HCC patients and is involved in autophagy regulation in HCC cells.
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Stiuso
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Naples, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Potenza
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Lombardi
authors.affiliation: Department of Biology, University "Federico II" of Naples, Naples, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Ferrandino
authors.affiliation: Department of Biology, University "Federico II" of Naples, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Monaco
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zappavigna
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vanacore
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Mosca
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Naples, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Castiello
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Porto
authors.affiliation: Medical Oncology Day Hospital Unit, San Giovanni di Dio Hospital, Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Addeo
authors.affiliation: Medical Oncology Day Hospital Unit, San Giovanni di Dio Hospital, Naples, Italy.
authors.forename: Salvatore Del
authors.initials: SD
authors.lastname: Prete
authors.affiliation: Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: De Vita
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Naples, Italy.
authors.forename: Aniello
authors.initials: A
authors.lastname: Russo
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia