<p>Long Non-Coding RNA TUG1 Promotes Cell Proliferation and Inhibits Cell Apoptosis, Autophagy in Clear Cell Renal Cell Carcinoma via MiR-31-5p/FLOT1 Axis</p>

Abstract

Purpose: Clear cell renal cell carcinoma (ccRCC) is a common urological carcinoma in adults. Long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) has been reported to be involved in the progression of diverse human cancers, including renal cell carcinoma (RCC). However, the biological mechanism of TUG1 was rarely reported in ccRCC. Methods: The levels of TUG1, microRNA miR-31-5p and flotillin 1 (FLOT1) in ccRCC tissues and cells were detected by qRT-PCR. The interactions between miR-31-5p and TUG1 or FLOT1 were predicted by starBase v2.0 and TargetScan, respectively, which were further validated by RIP assay and RNA pull-down assay. Cell counting kit-8 (CCK-8), flow cytometry and Western blot were used to assess the effects of TUG1 on cell viability, apoptosis rate and the relative protein expression levels in ccRCC cells. In addition, the xenograft tumor assay was conducted to further verify the functions of TUG1 in ccRCC in vivo. Results: TUG1 was dramatically up-regulated in ccRCC tissues and cells. TUG1 silencing inhibited cell proliferation and promoted cell apoptosis, autophagy in 786-0 and A498 cells. In addition, TUG1 depletion repressed tumor growth in vivo. Moreover, miR-31-5p was validated as a direct target of TUG1, and microRNA miR-31-5p inhibitor mitigated the effects of TUG1 knockdown on ccRCC progression. Furthermore, FLOT1 was verified to be negatively interacted with miR-31-5p. FLOT1 overexpression attenuated miR-31-5p-mediated inhibitory effect on cell proliferation and promotion effects on cell apoptosis, autophagy. The restoration experiment implicated that TUG1 positively modulated FLOT1 expression by sponging miR-31-5p. Conclusion: All data demonstrated that TUG1 promotes cell proliferation and inhibits cell apoptosis and autophagy in ccRCC by miR-31-5p/FLOT1 axis, which may provide a therapeutic target for ccRCC patients.

Long non-coding RNA ARAP1-AS1 contributes to cell proliferation and migration in clear cell renal cell carcinoma via the miR-361-3p/placental growth factor axis

“…Cell apoptosis was detected using the Annexin V-FITC cell apoptosis kit (Beyotime, China) according to a previously described method [ 36 ]. After transfection, the cells were collected and washed with PBS.…”

Role of Metabolic Reprogramming of Long non-coding RNA in Clear Cell Renal Cell Carcinoma

“…In addition, LncRNAs inhibit miRNA activity. For example, Lv D et al revealed that Taurine- Upregulated gene 1 (TUG1) is a 7.1-KB lncRNA located on chromosome 22q12, as ceRNA to isolate Mir-31-5p and promote flotillin 1 (FLOT1) to participate in cell membrane structure and mediate intercellular signal transduction 75 . FLOT1 is a lipid raft marker protein, and its n-terminal residues at position 1 to 185 constitute an SPFH (Stomatin, Prohibitin, Flotillin, Hflk/C) domain, which is palmitoylated at C34 site and associated with its localization in lipid raft 76 .…”

LncRNA HCG18 Promotes Clear Cell Renal Cell Carcinoma Progression by Targeting miR-152-3p to Upregulate RAB14

“…For example, lncRNA TUG1 facilitated the proliferation of ccRCC cells by targeting miR-31-5p and regulating FLOT1 expression. 8 LncRNA DARS-AS1 promoted the tumorigenesis of ccRCC through the miR-194-5p / DARS axis. 9 Recently, a cancer-related lncRNA HCG18 was identified to participate in several malignant cancers, such as bladder cancer, gastric cancer, and nasopharyngeal carcinoma.…”