Dataset Information

Steroid receptor RNA activator inhibits the migration, invasion and stemness characteristics of renal cell carcinoma cells

ABSTRACT: Renal cell carcinoma (RCC) has a high mortality rate among urological malignancies, and its underlying mechanisms remain unclear. Steroid receptor RNA coactivator (SRA) belongs to the long non-coding RNAs (lncRNAs) and has been demonstrated to be closely related to various types of cancer. In the present study, the decreased expression level of SRA was first confirmed in RCC tissues and cell lines by RT-qPCR. Using knockdown or overexpression systems, it was then found that SRA inhibited the proliferation of RCC cell lines and promoted their apoptosis. In addition, SRA suppressed the migration and invasion, and altered EMT-related markers in RCC cells. More importantly, it was demonstrated that SRA reduced percentage of CD44+/CD24? cells and the sphere-forming efficiency. SRA also attenuated the expression levels of CD44, SOX-2, ABCG2 and OCT-4, which are all associated with cancer cell stemness characteristics. Although SRA increased the phosphorylation of extracellular-regulated protein kinase (ERK), the ERK1/2 pathway could not further interfere with the alteration of EMT-related markers mediated by SRA. Notably, the ERK inhibitor, PD98059, abolished ERK1/2 phosphorylation, whereas it did not exert any marked effects on cell proliferation and EMT-related markers mediated by SRA. Taken together, the findings of the present study indicate that SRA is an important molecule that inhibits the migration, invasion and stem cell characteristics of RCC cells; the ERK signaling pathway may not be involved in this process.

SUBMITTER: Zhang C

PROVIDER: S-EPMC7521558 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Retinoblastoma (RB) is one of the most common forms of childhood intraocular cancer. While the occurrence of RB is traditionally associated with dysregulation of the RB1 gene, efforts have been made to assess the role of several other pathways that may result in RB. The Notch signaling pathway has been identified as one of the sentinel pathways in retinal development and has been indicated to serve as a tumor suppressor. However, epigenetic modifications of the Notch signaling pathway, and their consequences on tumor establishment and progression, have received little attention. The present study attempted to elucidate the microRNA (miR)-mediated dysregulation of the Notch signaling pathway and its implications on tumor initiation. Upon recruitment of patients with RB (age, 4-25 months), the levels of miR-34b-5p were determined in tumor and adjacent healthy tissues. Simultaneously, the serum levels of miR-34b-5p were measured in tumor and healthy samples using reverse transcriptase-quantitative PCR (RT-qPCR). Binding of miR-34b-5p to Notch1 and Notch2 were confirmed bioinformatically. In vitro studies were performed in Y79 and Weri-Rb-1 RB cell lines. The cell lines were transfected with miR-34b-5p constructs and miR-34b-5p overexpression was confirmed using RT-qPCR. The impact of miR-34b-5p overexpression on cell growth and cancer stemness markers (Sox-2, Nanog, and CD133) was examined. The expression levels of Notch1 and Notch2 were evaluated in the presence of miR-34b-5p. The rescue of cell growth and cancer stemness phenotypes was evaluated by co-transfection of miR-34b-5p with Notch1 or Notch2. The results of the present study indicated that the expression levels of miR-34b-5p were reduced in patient tissues and serum samples compared with those in healthy tissues and samples. Notch1 and Notch2 expression level was negatively correlated with the expression level of miR-34b-5p. Overexpression of miR-34b-5p resulted in reduced cell proliferation, migration, invasion and cancer stemness compared with the control group. Further in vivo experiments confirmed the inhibitory effects of miR-34b-5p on RB cell proliferation. Upon co-transfection of miR-34b-5p with Notch1 or Notch2, these phenotypes were rescued with reversal of cell growth and tumor sphere formation. Collectively, the results indicated that miR-34b-5p functions as a tumor suppressor in RB via regulating the Notch signaling pathway. Therefore, miR-34b-5p may be explored for its utility as a therapeutic target in RB.

Dataset Information

Steroid receptor RNA activator inhibits the migration, invasion and stemness characteristics of renal cell carcinoma cells

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets