lncRNA ROR promotes the progression of renal cell carcinoma through the miR‑206/VEGF axis

Abstract

Renal cell carcinoma (RCC) is the most common kidney malignancy, responsible for ~80% of all cases in adults. The pathogenesis of RCC is complex, involving alterations at both the genetic and epigenetic levels. Numerous signaling pathways, such as PI3K/Akt/mTOR and Wnt-β-catenin have been demonstrated to be associated with the tumorigenesis and development of RCC. Long non-coding RNAs (lncRNAs) are functional RNA molecules involved in the initiation and progression of cancer, and investigating the effects of lncRNA could facilitate the development of novel treatments. The lncRNA regulator of reprogramming (ROR) is aberrantly expressed in a variety of tumors. However, its underlying mechanisms remain largely unknown. In the present study, ROR was found to be upregulated and microRNA (miR)-206 was found to be downregulated in RCC tissues and cells. Furthermore, the knockdown of ROR inhibited the proliferation, migration and invasion of RCC cells. It was found that ROR binds to miR-206, and that ROR-induced cell proliferation and metastasis were reversed by the overexpression of miR-206. In addition, the levels of miR-206 and ROR were negatively correlated in RCC tissues. Furthermore, the overexpression of miR-206 notably suppressed the proliferation, migration and invasion of RCC cells, and these effects were enhanced by the knockdown of vascular endothelial growth factor (VEGF); cell growth and metastasis induced by miR-206 inhibitors could be reversed by the knockdown of VEGF. In addition, the expression levels of miR-206 and VEGF were inversely correlated in RCC samples. In summary, the results of the present study revealed that ROR was upregulated in RCC tissues, which promoted tumor progression by regulating the miR-206/VEGF axis. The present findings provided a novel insight into the potential functions of ROR in RCC, and the ROR/miR-206/VEGF pathway may be a promising therapeutic target for the treatment of patients with RCC.

Long noncoding RNA-regulator of reprogramming alleviates hypoxia-induced cerebral injury in mice model and human via modulating apoptosis complexes

“…Apoptosis of vascular cells contributes to the arterial architecture, especially when coordinated with matrix turnover and proliferation of vascular cells. Furthermore, studies have proven that ROR was also involved in vascular cell proliferation by regulating the expression of vascular endothelial growth factor (Shi et al, 2019). These results all indicate that ROR might be used as an agent to reverse vascular damage.…”

miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer

“…The role of miR-206 in cancers is complicated and controversial. Decreased expression of miR-206 was found in rhabdomyosarcoma [ 26 ], lung cancer [ 28 ], ER + breast cancer [ 29 , 30 ], renal cell carcinoma [ 31 ], ER alpha + endometrioid adenocarcinoma [ 32 ], hepatocellular carcinoma [ 33 , 34 ] and glioma [ 35 ]. Upregulation of miR-206 inhibits the migration, invasion and proliferation of breast cancer [ 30 ], renal cell carcinoma [ 31 ], glioma [ 35 ], and head and neck squamous cell carcinoma [ 31 ], suggesting a tumor suppressor role of miR-206.…”

“…Decreased expression of miR-206 was found in rhabdomyosarcoma [ 26 ], lung cancer [ 28 ], ER + breast cancer [ 29 , 30 ], renal cell carcinoma [ 31 ], ER alpha + endometrioid adenocarcinoma [ 32 ], hepatocellular carcinoma [ 33 , 34 ] and glioma [ 35 ]. Upregulation of miR-206 inhibits the migration, invasion and proliferation of breast cancer [ 30 ], renal cell carcinoma [ 31 ], glioma [ 35 ], and head and neck squamous cell carcinoma [ 31 ], suggesting a tumor suppressor role of miR-206. Increased expression of miR-206 was found in breast cancer [ 30 , 36 ], esophageal carcinoma [ 37 ] and some soft tissue sarcomas [ 38 ], and high miR-206 expression was related to the poor prognosis of breast cancer [ 36 ] and esophageal carcinoma patients [ 37 ].…”

Long non‑coding RNA PLK1S1 was associated with renal cell carcinoma progression by interacting with microRNA‑653 and altering C‑X‑C chemokine receptor 5 expression

“…For example, Yang et al (28) found that the lncRNA TUG1 acted as a ceRNA of miR-196a to accelerate the proliferation, migration and invasion of RCC. Shi et al (29) demonstrated that the lncRNA ROR sponged miR-206 to promote RCC progression through increasing the protein expression level of VEGF. Furthermore, Xie et al (17) demonstrated that hsa_circ_0004771 facilitated the proliferation and inhibited apoptosis in breast cancer by functioning as a ceRNA of miR-653 to regulate the ZEB2 signaling pathway.…”