Direct targeting sperm-associated antigen 9 by miR-141 influences hepatocellular carcinoma cell growth and metastasis via JNK pathway

Abstract

BackgroundThe aberrant expression of sperm-associated antigen 9 (SPAG9) is associated with numerous cancers, including hepatocellular carcinoma (HCC). The exploration of molecules and mechanisms regulating SPAG9 expression may provide new options for HCC therapy.MethodsMiRNA target prediction programs were used to explore SPAG9-targeted miRNAs. SPAG9 and miR-141 expression were detected in HCC tissues and cell lines by Western blot and real-time PCR. Dual-luciferase reporter assay was utilized to validate SPAG9 as a direct target gene of miR-141. Cell proliferation, invasion, and migration assays were used to determine whether miR-141-mediated regulation of SPAG9 could affect HCC progression.ResultsAn inverse correlation was observed between SPAG9 and miR-141 expression in HCC tissues and cell lines. Dual-luciferase reporter assay further showed that SPAG9 was a direct target gene of miR-141. The ectopic expression of miR-141 could markedly suppress SPAG9 expression in HCC cells. MiR-141 overexpression also resulted in significantly reduced cell proliferation, invasion, and migration, and imitation of the SPAG9 knockdown effects on HCC cells. Furthermore, SPAG9 restoration in miR-141-expressing cells sufficiently attenuated the tumor-suppressive effects of miR-141. Finally, JNK activity was found to be reduced by miR-141 overexpression the same way as by SPAG9 silencing. The overexpression of SPAG9 lacking its 3′-UTR significantly restored JNK activity and its downstream genes in miR-141-transfected HCC cells.ConclusionMiR-141 suppression may cause aberrant expression of SPAG9 and promote HCC tumorigenesis via JNK pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0289-z) contains supplementary material, which is available to authorized users.

Serum Expression Levels of miR-141 and miR-215 for Differentiation between Liver Cirrhosis, Chronic Hepatitis C and Hepatocellular Carcinoma Patients

“…These data indicate a tumor suppressive role for miR-141 in HCC patients and so its decreased expression levels indicate progressive or increased severity of HCC. In support of this assumption, Lou et al [34] found MiR-141 over expression resulted in significantly reduced cell proliferation, invasion, and migration effects on HCC cells.…”

Roles of the MST1-JNK signaling pathway in apoptosis of colorectal cancer cells induced by Taurine

“…Other studies have shown that the c-Jun N-terminal kinase (JNK) signaling pathway is involved in cell proliferation and differentiation. Its dysfunction can cause ischemia/reperfusion injury [6], diabetes [7], or tumors [8]. Thus, the JNK signaling pathway has become a potential clinical molecular therapeutic target.…”

Identification and Characterization of MicroRNAs in the Liver of Blunt Snout Bream (Megalobrama amblycephala) Infected by Aeromonas hydrophila

“…Several differentially expressed miRNAs have been found to be immune-related in mammals, such as miR-148/152, miR-101a, miR-141/200c, miR-146b, miR-217 and miR-375 [50,51,52,53,54,55,56]. A previous study demonstrated that the miR-148 and miR-152, two members of miR-148 family, were significantly increased in dendritic cells by TLR agonists, which inhibited the up-regulation of MHC II expression and the production of cytokine via targeting CaMKIIα, and might contribute to immune homeostasis [50].…”

“…miR-141 and miR-200c, belonging to the highly conserved miR-200 family, whose members are considered as tumor suppressors [52], can promote the mesenchymal-epithelial transition, and inhibit cell invasion by suppressing the Zeb2 and Snail1 transcriptional repressor complexes [53]. In addition, miR-200b/c and miR-217 regulate the expression of mortalin and the quantity of MACs (complement membrane attack complex) deposited on the target cells during complement activation to resist complement membrane attack [55], and the decreased miR-375 can activate JAK2-STAT3 pathway and promote the proliferation and migration of gastric epithelial cells in response to Helicobacter pylori infection [56].…”