<p>Long Non-Coding RNA DARS-AS1 Contributes to Prostate Cancer Progression Through Regulating the MicroRNA-628-5p/MTDH Axis</p>

Abstract

Purpose DARS antisense RNA 1 (DARS-AS1) is a long non-coding RNA that has been validated as a critical regulator in several human cancer types. Our study aimed to determine the expression profile of DARS-AS1 in prostate cancer (PCa) tissues and cell lines. Functional experiments were conducted to explore the detailed roles of DARS-AS1 in regulating PCa carcinogenesis. Furthermore, the detailed mechanisms by which DARS-AS1 regulates the oncogenicity of PCa cells were uncovered. Methods Reverse transcription quantitative polymerase chain reaction was performed to analyze DARS-AS1 expression in PCa tissues and cell lines. Cell Counting Kit-8 assays, flow cytometry analyses, Transwell assays, and tumor xenograft experiments were conducted to determine the regulatory effects of DARS-AS1 knockdown on the malignant phenotype of PCa cells. Bioinformatics analysis was performed to identify putative microRNAs (miRNAs) targeting DARS-AS1, and the direct interaction between DARS-AS1 and miR-628-5p was verified using RNA immunoprecipitation and luciferase reporter assays. Results DARS-AS1 was highly expressed in PCa tissues and cell lines. In vitro functional experiments demonstrated that DARS-AS1 depletion suppressed PCa cell proliferation, promoted cell apoptosis, and restricted cell migration and invasion. In vivo studies revealed that the downregulation of DARS-AS1 inhibited PCa tumor growth in nude mice. Mechanistic investigation verified that DARS-AS1 functioned as an endogenous miR-628-5p sponge in PCa cells and consequently promoted the expression of metadherin (MTDH). Furthermore, the involvement of miR-628-5p/MTDH axis in DARS-AS1-mediated regulatory actions in PCa cells was verified using rescue experiments. Conclusion DARS-AS1 functioned as a competing endogenous RNA in PCa by adsorbing miR-628-5p and thereby increasing the expression of MTDH, resulting in enhanced PCa progression. The identification of a novel DARS-AS1/miR-628-5p/MTDH regulatory network in PCa cells may offer a new theoretical basis for the development of promising therapeutic targets.

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

“…Several variants, mutations, or even genomic rearrangements (TMPRSS2-ERG fusion is the most common in human prostate cancer, but is absent in small cell carcinoma of the bladder) are involved in pathophysiological situations correlated with AR signaling pathways; the complex interaction of each protein in a specific context may lead to different results, and represents a new pharmacological target for these pathologies, including bladder cancer [29]. New strategies that modulate AR signaling are developing, as demonstrated in the studies with long noncoding RNAs (lncRNAs), microRNAs, enhancer RNAs (eRNAs), and others [30][31][32][33]. The AR interacts with enzymes (cofactors) involved in the regulation of histone methylation, such as lysine-specific demethylase 1 (LSD1), KDM4B, KDM5B, KDM7A, EZH2, SMYD3 and PRMT5.…”

Identification of a novel competing endogenous RNA network linked to the prognosis of prostate cancer

“…Additionally, mounting evidence indicates the involvement of the ceRNA network in PCa regulation. Fan et al suggested that lncRNA DARS1 Antisense RNA 1 (DARS-AS1) promotes PCa development via the DARS-AS1/miR-628-5p/MTDH ceRNA network [20]. Zhang et al identi ed that lncRNA OIP5-AS1 operates via a ceRNA mechanism in PCa by adsorbing miR-128-3p, leading to increased expression of SLC7A11 and hence promoting PCa progression and ferroptosis resistance [21].…”

Treatment-emergent and trajectory-based peripheral gene expression markers of antidepressant response

“…Unlike the protein-coding genes above, DARS-AS1 is a long noncoding RNA (lncRNA). The majority of studies investigating this lncRNA have been related to its role in cancer, where it acts to regulate the expression of several microRNAs, including miR-129, miR-194-5p, miR-532-3p, and miR-628-5p [ 38 – 41 ], as well as the protein RNA-binding motif protein 39 (RBM39) [ 42 ]. As a number of studies have highlighted the importance of microRNAs in antidepressant response [ 43 , 44 ], it seems plausible that the role of DARS-AS1 in escitalopram response involves modulation of microRNA expression.…”