MALAT1 accelerates the development and progression of renal cell carcinoma by decreasing the expression of miR‐203 and promoting the expression of BIRC5

Abstract

| INTRODUC TI ONRenal cell carcinoma (RCC) is a common cancer that accounts for 2%-3% of all cancerous diseases in adults. 1 There are approximately 65 000 cases of RCC each year, and RCC is the eighth most common cause of cancer mortality. 2 RCC affects quality of life and life expectancy and has important health and economic implications related to metabolic syndromes, increased cardiovascular risk and end-stage kidney disease. 3 In addition, clear cell renal cell carcinoma (ccRCC) is the most universal subtype of RCC, accounting for approximately 75% of RCC. Furthermore, the morbidity and mortality rates of RCC are rising globally. 4 Besides traditional surgery, RCC is resistant to the other forms of therapies chemotherapy and radiotherapy. The 5-year survival rate of RCC is approximately 55%, while the 5-year survival rate of metastatic RCC is approximately 10%. 5 Patients with metastatic RCC are faced with a depressing prognosis and limited therapeutic options. The median survival time in a recent cohort study was only 1.5 years, and the survival rate was less than 10% in patients who survived 5 years. 6 Thus, it is vital to study the molecular basis of RCC to design novel therapeutic drugs to improve survival rates.Abstract Objective: We aimed to investigate the roles of the lncRNA MALAT1 in renal cell carcinoma (RCC) progression. Methods: qRT-PCR was used for the assessment of BIRC5, miRNA-203 and MALAT1 expression. Furthermore, the targeted relationships between miR-203 and BIRC5, as well as MALAT1 and miR-203, were predicted by the miRanda/starBase database and verified by dual-luciferase reporter gene assay. The effects of MALAT1, miRNA-203 and BIRC5 on cell proliferation, cell cycle, cell apoptosis, cell invasion and cell migration were studied by using CCK-8, flow cytometry, transwell and wound healing assays, respectively. In addition, the effects of MALAT1 on RCC tumorigenesis were evaluated in vivo by nude mouse tumorigenesis. Results: The expression levels of BIRC5 and MALAT1 were higher in RCC tissues and cell lines than in adjacent normal tissues and a normal renal cortex proximal tubule epithelial cell line. In contrast, the expression of miRNA-203 in RCC tissues and cell lines was higher than that in adjacent normal tissues and a normal renal cortex proximal tubule epithelial cell line. BIRC5 and MALAT1 promoted cell proliferation yet decreased the percentage of RCC cells at G0/G1 phase. Conclusions:Our study demonstrated that MALAT1 functions as a miR-203 decoy to increase BIRC5 expression in RCC.

Long non-coding RNA MALAT1 facilitates the tumorigenesis, invasion and glycolysis of multiple myeloma via miR-1271-5p/SOX13 axis

“…The oncogenic role of MALAT1 in the progression of human cancers has gradually emerged. For instance, Zhang et al announced that MALAT1 accelerated the progression of renal cell carcinoma via the regulation of the miR-203/BIRC5 axis (Zhang et al 2019). Sun et al claimed that MALAT1 expression was elevated and regulated cell proliferation and apoptosis in ovarian cancer through directly targeting miR-503-5p (Sun et al 2019).…”

LINC00511 exacerbated T-cell acute lymphoblastic leukemia via miR-195-5p/LRRK1 axis

“…Mechanistically, a multitude of researches claimed that lncRNA could function as a competitive endogenous RNA (ceRNA) by sequestering micro RNA (miRNA) to release target gene, and thereby modulate the biological processes in tumors. For instances, MALAT1 accelerates cell proliferation and migration of renal cell carcinoma cells by sponging miR-203 and increasing BIRC5 expression [16]. SNHG5/miR-26a/SOX2 axis promotes proliferation of chondrocyte in osteoarthritis [17].…”

Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis

“…Zheng et al [25] found that lncRNA AB209371 accelerated the development and progression of ovarian carcinoma by suppressing miR-203 expression. MALAT1 promoted the development of renal cell carcinoma by reducing the expression of miR-203 expression [26]. Furthermore, miR-203 has been proven to be involved in the expression of several cancerrelated factors.…”