DGUOK-AS1 promotes cervical squamous cell carcinoma progression by suppressing miR-499a-5p that targets SPRR1B in vitro.

PURPOSE: Cervical squamous cell carcinoma (CESC) is the most common cancer type of cervical cancer, which threatens women's life seriously. LncRNA DGUOK-AS1has been reported to promote the biologic processes of CESC. We aim to figure out the role of DGUOK-AS1-miR-499a-5p-SPRR1B axis in modulating the CESC progression in vitro. METHODS: The levels of DGUOK-AS1, miR-499a-5p, and SPRR1B in CESC tissues and cells were examined by RT-qPCR. The interaction of DGUOK-AS1-miR-499a-5p-SPRR1B was verified by luciferase assay. Inhibition of DGUOK-AS1, miR-499a-5p, and SPRR1B was applied for exploring the biological function based on detection of cell viability, proliferation, migration, and apoptosis in CESC SiHa and HeLa cells. RESULTS: DGUOK-AS1 and SPRR1B expressions were obviously elevated, whereas the expression of miR-499a-5p was reduced in both CESC tissues and cells. Silencing of DGUOK-AS1 attenuated cell growth and boosted apoptosis of CESC cells. Notably, DGUOK-AS1 inhibited miR-499a-5p to release SPRR1B, which significantly accelerated the development of CESC. CONCLUSION: DGUOK-AS1sponging miR-499a-5p facilitated CESC cells progression by releasing SPRR1B in vitro. It provides a new sight for the treatment of CESC patients involving DGUOK-AS1-miR-499a-5p-SPRR1B.

MicroRNA-497 suppresses cell proliferation and induces apoptosis through targeting PBX3 in human multiple myeloma.

Aberrant expression of microRNA-497 (miRN-497) is implicated in development and progression of multiple types of cancers. However, the biological function and underlying mechanism of miR-497 in multiple myeloma (MM) remains unclear. Thus, we studied the potential biological roles of miR-497 in MM. The expression of miR-497 was examined in multiple myeloma and normal plasma cells by qRT-PCR. Biological functions of miR-497 were analyzed using cell proliferation, colony formation, cell cycle, apoptosis and luciferase assays in vitro, as well as via tumorigenicity in vivo analysis. Here, we observed reduced expression of miR-497 in MM plasma samples and cell lines. Ectopic expression of miR-497 dramatically suppressed cell proliferation and clonogenicity, as well as induced cell arrest at G0/G1 stage and apoptosis in vitro. Mechanistic investigation assays showed that Pre-B-cellleukemia transcription factor 3 (PBX3) was a novel and direct downstream target of miR-497. Interestingly, overexpression of PBX3 partially reverted the effect of miR-497 in MM cells. In xenograft model, overexpression of miR-497 inhibited tumorigenicity by repressing PBX3. These findings collectively suggested that miR-497 functioned as tumor suppressor in MM by directly targeting PBX3, supporting its utility as a novel and potential therapeutic agent for MM therapy.

PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b.

miR-125b has essential roles in coordinating tumor proliferation, angiogenesis, invasiveness, metastasis and chemotherapy recurrence. In ovarian cancer miR-125b has been shown to be downregulated and acts as a tumor suppressor by targeting proto-oncogene BCL3. PPARγ, a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of proliferation and induction of differentiation and apoptosis by targeting the tumor related genes. However, it is unclear whether miR-125b is regulated by PPARγ in ovarian cancer. In this study, we demonstrated that the miR-125b downregulated in ovarian cancer tissues and cell lines. Ligands-activated PPARγ suppressed proliferation of ovarian cancer cells and this PPARγ-induced growth inhibition is mediated by the upregulation of miR-125b. PPARγ promoted the expression of miR-125b by directly binding to the responsive element in miR-125b gene promoter region. Thus, our results suggest that PPARγ can induce growth suppression of ovarian cancer by upregulating miR-125b which inhibition of proto-oncogene BCL3. These findings will extend our understanding of the function of PPARγ in tumorigenesis and miR-125b may be a therapeutic intervention of ovarian cancer.

Lentivirus vector-mediated mitofusin-2 overexpression in rat ovary changes endocrine function and promotes follicular development in vivo.

The aim of the present study was to evaluate the expression and effect of rat mitofusin-2 (rMfn2) in the ovaries and other organs in rats. Rat models were developed by the intraovarian microinjection of an rMfn2-overexpressing lentiviral vector. Lenti-green fluorescent protein (GFP)-rMfn2 was microinjected into rat ovaries at a dosage of 2×106 tuberculin units virosome (n=25) and lenti-GFP was microinjected as a control (n=25). The expression of rMfn2 in the ovaries and other tissues was observed by fluorescence microscopy on days 7, 15, 30, 45 and 60 after the microinjection (n=5/day from each group). The serum levels of estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined by radioimmunoassay. Western blotting was used for the quantitative analysis of the expression of rMfn2 and the progesterone receptor (PR), estradiol receptor (ER), luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR). The expression of rMfn2 was detected on day 7 after infection, increased with time and was maintained efficiently until day 60. In addition, rMfn2 was highly expressed in the fallopian tubes, uterus, cardiac muscle, liver and kidney, but expressed at a low level in adipose tissue. The serum levels of E2 and P in the model group were significantly increased compared with those in the control group, whereas the FSH and LH levels showed no significant difference between groups. The expression levels of the ER and PR in the model group were higher than those in the control group; however, no significant difference was observed between groups for the expression levels of LHR and FSHR. These findings suggest that the intraovarian microinjection of lenti-GFP-rMfn2 resulted in a significant time-dependent overexpression of rMfn2 in various organs, and that rMfn2 overexpression in rat ovaries changed the endocrine function and promoted follicular development.