Downregulation of lncRNA CASC2 by microRNA-21 increases the proliferation and migration of renal cell carcinoma cells

Abstract

Several long non-coding RNAs (lncRNAs) have been identified that may have a crucial role in tumor progression and metastasis. The lncRNA cancer susceptibility candidate 2 (CASC2) has previously been reported to act as a tumor suppressor gene in glioma and colorectal cancer. However, the expression and function of CASC2 in renal cell carcinoma (RCC) remains to be elucidated. The present study confirmed that CASC2 was downregulated in human RCC tissues and human RCC cell lines (786‑O and A498). Restoration of CASC2 expression via transfection with a pcDNA3.1(+)‑CASC2 vector was able to inhibit cell proliferation and migration in 786‑O and A498 cells, as compared with in the cells transfected with a pcDNA3.1(+) empty vector. MicroRNA‑21 (miR‑21) has been reported to be upregulated in human RCC tissues and cell lines, and is associated with the malignant progression of RCC. In the present study, bioinformatics analysis and dual‑luciferase reporter assays confirmed that CASC2 was a direct target gene of miR‑21. miR‑21 was able to decrease the expression of CASC2 in 786‑O and A498 cells. Furthermore, overexpression of miR‑21 partly abrogated CASC2‑mediated inhibition of 786‑O and A498 cell proliferation and migration. The present study provides evidence indicating that CASC2 targeted by miR‑21 acts as a tumor suppressor in RCC. Therefore, CASC2 may be considered a novel target for the diagnosis and treatment of RCC.

LncRNA CASC2 Interacts With miR‐181a to Modulate Glioma Growth and Resistance to TMZ Through PTEN Pathway

“…Another lncRNA, UCA1, enhances 5‐fluorouracil resistance in colorectal cancer by inhibiting miR‐204‐5p [Bian et al, ]. Low expression of CASC2 increases the proliferation and migration of renal cell carcinoma cells, and indicates a poor prognosis in non‐small cell lung cancer [Cao et al, ; He et al, ]. In the present study, we indicated the low expression of CASC2 in glioma, and its relation with poorer clinicopathologic features.…”

Molecular Crosstalking among Noncoding RNAs: A New Network Layer of Genome Regulation in Cancer

“…Interestingly, GAS5 also negatively regulated miR-21 at the posttranscriptional level through the RISC complex, suggesting the existence of a reciprocal negative feedback loop between GAS5 and miR-21 [104]. In two different studies on renal cell carcinoma and glioblastoma, it has been shown that miR-21 targeted and suppressed the expression of the tumor suppressor lncRNA CASC2 (cancer susceptibility candidate 2) in an AGO2-dependent manner [105, 106]. Indeed, the overexpression of miR-21 abrogated the inhibition of proliferation, migration, and the induction of apoptosis promoted by CASC2.…”

Down-regulation of lncRNA CASC2 promotes cell proliferation and metastasis of bladder cancer by activation of the Wnt/β-catenin signaling pathway

“…Wang et al demonstrated that CASC2 plays a tumor suppressive role in glioma via negative regulation of miR-21 [14]. In addition, low expression of long noncoding RNA CASC2 indicates a poor prognosis and regulates cell proliferation in non-small cell lung cancer [15] and renal cell carcinoma cells [16]. Besides, the long noncoding RNA CASC2 functions as a competing endogenous RNA by sponging miR-18a in colorectal cancer [17].…”