Long noncoding RNA lung cancer associated transcript 1 promotes proliferation and invasion of clear cell renal cell carcinoma cells by negatively regulating miR‐495‐3p

Abstract

Recently, long noncoding RNAs have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). Here, we focused on the long noncoding RNA lung cancer associated transcript 1 (LUCAT1) based on clear cell RCC (ccRCC) the cancer genome atlas (TCGA) data. However, whether aberrant expression of LUCAT1 in ccRCC is correlated with malignancy, metastasis or prognosis has not been elucidated. In the current study, we found that the expression of LUCAT1 was upregulated in ccRCC tissues and cancer cell lines. Upregulated LUCAT1 was positively correlated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, higher smoking frequency, nodal metastasis and shorter overall survival in patients with ccRCC. Inhibition of LUCAT1 by small interfering RNA reduced cell proliferation and invasion of ccRCC cells in vitro. In vivo assay showed that the tumor volume and weight were lower in the group of LUCAT1 inhibition than that in the control group. We then found that LUCAT1 directly bound and inhibited the expression of micoRNA-495-3p (miR-495-3p), which subsequently regulated the expression of special adenine-thymine (AT)-rich DNA-binding protein 1 (SATB1). Collectively, LUCAT1 was critical for proliferation and invasion of ccRCC cells by regulating miR-495-3p and SATB1. Our findings indicated that LUCAT1 and miR-495-3p may offer potential novel therapeutic targets of treatment of ccRCC.

LUCAT1 promotes colorectal cancer tumorigenesis by targeting the ribosomal protein L40‐MDM2‐p53 pathway through binding with UBA52

“…Lung cancer‐associated transcript 1 is located on chromosome 5 and was first observed in the airway epithelium of smokers and in various cancer cell lines . In addition to lung cancer, LUCAT1 has also been reported to be involved in esophageal cancer, renal cell carcinoma, and cisplatin‐resistant ovarian cancer . Like other lncRNAs, LUCAT1 participates in carcinogenesis and cancer progression by regulating gene expression through chromatin modification, transcription, and post‐transcriptional procession.…”

<p>miR-495-3p inhibits the cell proliferation, invasion and migration of osteosarcoma by targeting C1q/TNF-related protein 3</p>

“…It has been reported that miR-495-3p may have an oncogenic or anticancer effect in several cancers. For instance, miR-495-3p inhibits proliferation and invasion in clear cell renal cell carcinoma cells 12. miR-495-3p serves as a tumor suppressor by regulating multiple epigenetic modifiers in gastric carcinogenesis 13.…”

Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response

“…Previous reports demonstrated that LUCAT1 is often upregulated in several types of cancer cells and promotes the proliferation, invasion or migration of these cells from many cancer types including CRC [23][24][25][26][27][28][29][30][31][32][33]. LUCAT1 can act as microRNA sponge [25,[29][30][31][32], or bind proteins, such as DNMT1, to regulate their stabilities or activities [23,24,26,28]. In the present study, we identified that hypoxia-induced LUCAT1, mainly located in the nucleus of CRC cells, which is physically interacts with an RNA-binding protein PTBP1 and regulates mRNA alterative splicing pathway.…”