Long Non-coding RNA GAS5 Functions as a Tumor Suppressor in Renal Cell Carcinoma

Abstract

Background: Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. We aimed to explore whether the expression of Long Non-Coding RNA (LncRNA) growth arrest-specific transcript 5 (GAS5) is associated with RCC genesis. Methods: We selected twelve clinical samples diagnosed for renal clear cell carcinoma and found that the LncRNA GAS5 transcript levels were significantly reduced relative to those in adjacent unaffected normal renal tissues. Results: In addition, expression of GAS5 was lower in the RCC cell line A498 than that in normal renal cell line HK-2. Furthermore, using functional expression cloning, we found that overexpression of GAS5 in A498 cells inhibited cell proliferation, induced cell apoptosis and arrested cell cycling. At the same time, the migration and invasion potential of A498 cells were inhibited compared to control groups. Conclusion: Our study provided the first evidence that a decrease in GAS5 expression is associated with RCC genesis and progression and overexpression of GAS5 can act as a tumor suppressor for RCC, providing a potential attractive therapeutic approach for this malignancy.

LncRNA UCA1 promotes renal cell carcinoma proliferation through epigenetically repressing p21 expression and negatively regulating miR-495

“…Recent reports suggest that lncRNAs play an important role in regulation of diverse cellular processes such as cell growth and apoptosis and cancer metastasis. 5 Several lncRNAs have been reported to be participated in renal cancer, such as, Qiao et al 6 found that a decrease in lncRNA growth arrest-specific 5 (GAS5) expression was associated with RCC genesis and progression and overexpression of GAS5 can inhibit the RCC progression. A recent study indicated that LncRNA metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) could function as a competing endogenous RNA to regulate zinc finger e-box binding homeobox 2 (ZEB2) expression by sponging miR-200s in clear cell kidney carcinoma.…”

Long Non-coding RNAs are Differentially Expressed in Hepatocellular Carcinoma Cell Lines with Differing Metastatic Potential

“…The loss of GAS5 expression have been found in many types of tumors including melanoma, prostate cancers and breast but the concrete mechanism still needs further research (Smedley et al, 2000;Nupponen and Carpten, 2001;Mourtada-Maarabouni et al, 2009). In addition, the expression of GAS5 in Renal Cell Carcinoma specimens was obviously lower than that in adjacent normal tissues, and GAS5 can arrest cell cycling, induce cell apoptosis, also suppress cell migration and invasion (Qiao et al, 2013). These results suggest that GAS5 may have potential value to become a tumor marker for several tumors.…”

Long Non-coding RNAs and Drug Resistance

“…GAS5 can resist migration and invation as well as promote apoptosis in renal cell carcinoma (RCC) cells, a role as a tumor suppressor in RCC has also been demonstrated (Pickard et al, 2013;Qiao et al, 2013). Downregulation of GAS5 contributing to glucocorticoid resistance through alleviating sensitivity of tumor cells to apoptosis via suppressing glucocorticoid-mediated induction of several responsive genes like anti-apoptotic cellular inhibitor of apoptosis 2 (cIAP2) and serum/glucocorticoid-regulated kinase 1 (SGK1).…”