Non-coding RNA 886 promotes renal cell carcinoma growth and metastasis through the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway

Abstract

Non-coding RNA 886 (nc886) has been suggested to serve tumor-suppressing roles in several cancer cells. However, the expression pattern of nc886 and its function in renal cell carcinoma (RCC) has not been reported until now. The present study aimed to examine the expression of nc886 in human RCC tissues and to investigate the role of nc886 in RCC cell proliferation, apoptosis and invasion in vitro. Furthermore, whether nc886 exerts its function on RCC via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling was investigated. It was demonstrated that nc886 is overexpressed in human RCC tissues compared with normal tissues, as determined by reverse transcription-quantitative polymerase chain reaction analysis. The nc886 mimic and inhibitor were transfected into the A‑498 cells to overexpress or knock down nc886 expression. Cell proliferation, cell apoptosis rate and cell invasion ability were determined by MTT, flow cytometry and Transwell‑Matrigel invasion assays. The results demonstrated that nc886 overexpression promotes A‑498 cell proliferation and invasion, and inhibits cell apoptosis, while nc886 knockdown resulted in the opposite effects. Furthermore, nc886 could activate the JAK2/STAT3 signaling pathway in A‑498 cells. AG490, an inhibitor of JAK2, could attenuate the effects of nc886 on cell proliferation, apoptosis and invasion. In conclusion, to the best of our knowledge, the present study for the first time revealed the expression profile and the tumor‑promoting role of nc886 in RCC. nc886 affects RCC cell proliferation, apoptosis and invasion at least partially via the activation of JAK2/STAT3 signaling. This study may provide a useful therapeutic target for RCC.

Pan-Cancer chromatin analysis of the human vtRNA genes uncovers their association with cancer biology

“…Yet, vtRNA2-1 has been also proposed as an OG in ovarian, thyroid, endometrial, cervical and renal cancer (Ahn et al, 2018;Hu et al, 2017;Lee et al, 2016;Lei et al, 2017;Li et al, 2017;Yeganeh and Hernandez, 2020). In agreement with the functional data found by Lei et. al.…”

“…Furthermore, functional studies in LUSC, PRAD, ESCA and AML provided experimental support to that hypothesis (Cao et al, 2013;Fort et al, 2018;Lee et al, 2014a;Treppendahl et al, 2012). Yet, vtRNA2-1 has been also proposed as an OG in ovarian, thyroid, endometrial, cervical and renal cancer (Ahn et al, 2018;Hu et al, 2017;Lee et al, 2016;Lei et al, 2017;Li et al, 2017;Yeganeh and Hernandez, 2020). In agreement with the functional data found by Lei et.…”

“…Due to its importance for cancer biology, vtRNA2-1 transcriptional regulation was recently more investigated (Yeganeh and Hernandez, 2020). Various studies reported tissue specific roles of vtRNA2-1 in normal (Golec et al, 2019;Lee et al, 2019a;Miñones-Moyano et al, 2013;Sallustio et al, 2016;Suojalehto et al, 2014) and cancer tissue (Ahn et al, 2018;Fort et al, 2018;Hu et al, 2017;Im et al, 2020;Jeon et al, 2012a;Kunkeaw et al, 2012;Lee et al, 2011;Lee, 2015;Lee et al, 2016Lee et al, , 2014aLee et al, , 2014bLei et al, 2017;Li et al, 2017;Ma et al, 2020;Treppendahl et al, 2012) and epigenetic alterations of the locus have been described in different malignancies (Ahn et al, 2018;Cao et al, 2013;Fort et al, 2018;Helbo et al, 2015Helbo et al, , 2017Joo et al, 2018;Lee et al, 2014aLee et al, , 2014bPark et al, 2017;Romanelli et al, 2014;Treppendahl et al, 2012).…”

“…Then, its anti-proliferative and TSG function was described in prostate (Aakula et al, 2015;Fort et al, 2018;Ma et al, 2020), skin (Lee et al, 2019a), gastric (Lee et al, 2014b) and esophageal (Im et al, 2020;Lee et al, 2014a) and cholangiocarcinoma cells (Kunkeaw et al, 2012). Conversely, a pro-proliferative and anti-apoptotic oncogenic role was proposed for vtRNA2-1 in renal (Lei et al, 2017), ovarian (Ahn et al, 2018), thyroid (Lee et al, 2016), cervical (Li et al, 2017) and endometrial (Hu et al, 2017) tissues. A recent finding proposing a vtRNA2-1/PKR loss mediated doxorubicin cytotoxicity introduced a novel view about its contribution to chemotherapy response (Kunkeaw et al, 2019).…”

RNA polymerase III transcription as a disease factor

“…The nc886 gene is located within a CpG island and in all cases examined, down-regulation resulted from progressive methylation of the gene flanking sequences. In contrast, nc886 expression was increased in renal cell carcinoma (Lei et al 2017) and in thyroid (11 out of 37 tumors analyzed with an overexpression of >1.3, which tend to be the more aggressive tumors) (Lee et al 2016), endometrial (Hu et al 2017), and some ovarian (Ahn et al 2018) cancers. In human mammary epithelial cell lines that serve as models of early breast tumorigenesis, decreased or increased levels of nc886 were observed depending on the cell line, in the first case due to CpG hypermethylation and heterochromatin induction, and in the second case due to enhanced binding of MYC near the nc886 locus (Park et al 2017).…”