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.

• Authors: Chanjuan Zhang, Neng Zhu, Chan Liu, Hongtao Wu, Yantao Yin, Yaning Shi, Duanfang Liao, Li Qin
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 46 Issue 5 Pg. 1765-1776 (Nov 2020) ISSN: 1791-244X [Electronic] Greece
• PMID: 33000206 (Publication Type: Journal Article)

Chemical References

• RNA, Long Noncoding
• steroid receptor RNA activator

Topics

• Apoptosis (genetics)
• Carcinoma, Renal Cell (genetics, pathology)
• Cell Cycle (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Cell Survival (genetics)
• Down-Regulation (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Kidney Neoplasms (genetics, pathology)
• MAP Kinase Signaling System
• Models, Biological
• Neoplasm Invasiveness
• Neoplastic Stem Cells (metabolism, pathology)
• Phosphorylation
• RNA, Long Noncoding (genetics, metabolism)