Exosome-transmitted long non-coding RNA SENP3-EIF4A1 suppresses the progression of hepatocellular carcinoma

Abstract

Extracellular communication mediated by exosomes in a tumor microenvironment can substantially affect tumor progression. However, the effect of exosomal long non-coding RNA SENP3-EIF4A1 on hepatocellular carcinoma (HCC) is still unclear. In this study, SENP3-EIF4A1 expressions in patients with HCC and healthy controls were detected and compared. Results showed that SENP3-EIF4A1 was significantly reduced in HCC tissues and exosomes from the plasma of patients with HCC (P<0.05) and was primarily encapsulated by exosomes. The patients with HCC and the healthy controls could be distinguished using exosomal SENP3-EIF4A1 (AUC=0.8028). The transfer of exosomal SENP3-EIF4A1 secreted by normal cells to HCC cells stimulated apoptosis and weakened the invasion and migration abilities of HCC cells to suppress their malignant biological behavior (P<0.05). Additionally, exosomal SENP3-EIF4A1 was capable of inhibiting tumor growth in vivo and modulating the expression of ZFP36 by competitively binding to miR-9-5p. In conclusion, exosomal SENP3-EIF4A1 is a new favorable biomarker for clinically detecting HCC, and SENP3-EIF4A1 can be transmitted by exosomes from normal cells to HCC cells to inhibit the in vitro and in vivo development of HCC. Thus, exosomal SENP3-EIF4A1 is involved in the communication between normal cells and HCC cells during the onset of HCC.

The Biological Roles of Exosomal Long Non-Coding RNAs in Cancers

“… 29 Exosomal lncRNA SENP3-EIF4A1 sponging miR-9-5p protected ZFP36 from inhibiting the biological malignant behavior of HCC. 20 Exosomal lncRNA UCA1 of NSCLC promoted drug resistance to gefitinib by targeting FOSL2 through sponging miR-143. 45 …”

“…The exosomal lncRNA SENP3-EIF4A1 inhibited the progression of hepatocellular cancer (HCC) and the exosomal lncRNA SENP3-EIF4A1 sponging miR-9-5p protected ZFP36, inhibited the biological malignant behavior of HCC. 20 The lncRNA TCONS_00027227 activated by APC (TCNS_00027227), that is, lncRNA APC1, adenomatous polyposis coli (APC)-activated lncRNA APC1, in colorectal adenomatous polyposis inhibited the production of exosomes and reduced its stability through direct binding to Rab5b mRNA, inhibiting the growth, metastasis, and angiogenesis of colorectal cancer (CRC) cells. 21 The exosome secreted by SKOV3 cells inhibited the PTEN/AKT signal pathway by transduction of the lncRNA FAL1, inhibiting the metastasis of ovarian cancer cells in vivo and in vitro.…”

“…The exosomal lncRNA SENP3-EIF4A1 inhibited the progression of hepatocellular cancer (HCC) and the exosomal lncRNA SENP3-EIF4A1 sponging miR-9-5p protected ZFP36, inhibited the biological malignant behavior of HCC. 20 The lncRNA TCONS_00027227 activated by APC (TCNS_00027227), that is, lncRNA APC1, adenomatous polyposis coli (APC)-activated lncRNA APC1, in colorectal adenomatous polyposis inhibited the production of exosomes and reduced its stability through direct binding to Rab5b mRNA, submit your manuscript | www.dovepress.com…”

“…29 Exosomal lncRNA SENP3-EIF4A1 sponging miR-9-5p protected ZFP36 from inhibiting the biological malignant behavior of HCC. 20 Exosomal lncRNA UCA1 of NSCLC promoted drug resistance to gefitinib by targeting FOSL2 through sponging miR-143. 45 Exosomal lncRNAs can participate in tumorigenesis and development, chemotherapy resistance, angiogenesis, and radiosensitivity through a variety of pathways, especially through the ceRNA mechanism.…”

MicroRNAs from Liquid Biopsy Derived Extracellular Vesicles: Recent Advances in Detection and Characterization Methods

“…The internalization of the exosomes has been proven to influence recipient cells mainly due to the composition of the exosomal cargo [29]. "Signals" are encoded in the components of the exosomal cargo, consisting of fragmented nuclear DNA [30][31][32], mitochondrial DNA [33], proteins, growth factors [34] miRNAs [24,35], and long non-coding RNAs [36,37], making exosomes very important players in cell-to-cell communication. The exact mechanisms of how exosomal cargo is selected and loaded are still under constant discussion [38].…”