MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of noncoding RNAs. Here, we focused on the function and molecular mechanism of miR-1 and its potential clinical application in clear cell renal cell carcinoma (ccRCC). First, miR-1 was significantly downregulated in 87.8% renal cancer samples compared with corresponding noncancerous tissues (NCT), which was significantly associated with clinical stage, T classification and poor overall survival. Functional study demonstrated that enforced overexpression of miR-1 in renal cancer cells inhibited proliferation and metastasis in vitro and in vivo. Conversely, miR-1 inhibitor silencing miR-1 expression promoted cell proliferation and metastasis in ccRCC. CDK4, CDK6, Caprin1 and Slug were each directly targeted for inhibition by miR-1 and restoring their expression reversed miR-1-mediated inhibition of cell cycle progression and metastasis. Taken together, our findings established a tumor suppressive role for miR-1 in the progression of ccRCC by targeting CDK4, CDK6, Caprin1 and Slug and suggested miR-1 can be served as a novel potential therapeutic target for ccRCC.

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system, the pathogenesis of RCC is still unclear. It is reported that genetic variations in telomere length related-genes TERT and TERC are involved in the many types of cancers. However, little is known about the association between TERT and TERC polymorphisms and susceptibility to RCC risk. To solve this problem, a total of 293 patients with primary renal cell carcinoma and 459 healthy people were recruited in our study. Six SNPs of TERC and TERT were genotyped, and association analysis was performed. We found TERC-rs35073794 and TERT-rs10069690 were associated with an increased risk of RCC in an allele model. (OR =2.39, 95% CI = 0.99-5.80, p = 0.047; OR =1.39, 95% CI = 1.07-1.81, p = 0.014, respectively). The genotype "TC" of rs10069690 was associated with an increased risk of RCC in the genotype model. (OR =1.52, 95% CI = 1.11-2.08, p = 0.009).TERC-rs35073794 was associated with an increased risk of RCC in the codominant model. (OR =2.61, 95% CI = 1.01-6.76, p = 0.045). Rs10069690 was associated with an increased risk of RCC under the dominant model. (OR=1.44, 95% CI= 1.04-2.01, p = 0.03). Haplotype "CA" was found to be associated with a decreased risk of RCC while haplotype "TA" was associated with an increased risk of RCC without adjustment for gender, age and body mass index (BMI). (OR=0.07; 95% CI= 0.01-0.54; p=0.011; OR= 1.24; 95% CI= 0.92-1.65; p=0.013, respectively). Rs35073794, rs10936599 and rs10069690 were positively correlated with the age older than 55 (OR= 3.27, 95%CI= 1.08-9.93, p=0.031; OR= 1.56, 95%CI= 1.03-2.37, p= 0.034; OR= 4.94, 95%CI= 1.18-20.70, p= 0.022, respectively) with or without history of drinking(OR= 4.47, 95%CI= 0.99-20.25, p= 0.024; OR= 2.62, 95%CI= 1.13-6.08, p= 0.022; OR=2.44, 95%CI=1.03-5.78, p= 0.04, respectively) and clinical stage I/II RCC (OR=2.62, 95%CI=1.02-6.74, p= 0.045; OR= 2.23, 95%CI= 1.08-4.60, p= 0.028; OR= 1.63, 95%CI= 1.17-2.27, p= 0.014, respectively). Our study indicated a significant association between SNPs in the TERC, TERT and RCC risk in a Chinese Han population. It could be used as diagnostic and prognostic markers in clinical studies of renal cell carcinoma patients.

MicroRNAs, a kind of small non-coding RNAs, can regulate gene expression by targeting mRNAs for translational repression or degradation. Much evidence has suggested that miR-218 was a tumor suppressor in many human cancers including prostate cancer. However, the underlying role of miR-218 in tumor angiogenesis and the mechanisms in PCa and other cancers remains to be unclear. Here in this present study, we demonstrated that miR-218 inhibited the tumor angiogenesis of PCa cells in vitro and in vivo. RICTOR, the mTOR component 2, was a direct target of miR-218 and miR218-RICTOR-VEGFA axis was the mechanism inhibiting the tumor angiogenesis of PCa cells. RICTOR knockdown phenocopied miR-218 overexpression in inhibiting prostate cancer angiogenesis. Altogether, our findings indicate that down-regulation of miR-218 contributes to tumor angiogenesis through RICTOR/VEGFA axis in PCa, providing new insights into the potential mechanisms of PCa oncogenesis and revealing the potential of miR-218 as a useful serum biomarker and a new therapeutic target for human PCa.

Long non-coding RNAs (lncRNAs) exert critical regulatory roles in the development and progression of several cancers. Plasmacytoma variant translocation 1 (PVT1), an lncRNA, was shown to be upregulated in clear cell renal cell carcinoma (ccRCC) in our study, while Kaplan-Meier curve and Cox regression analysis showed that high expression of PVT1 was associated with poor overall survival (OS) and disease free survival (DFS) in ccRCC patients. In vitro experiments revealed that PVT1 promoted renal cancer cell proliferation, migration, and invasion, while in vivo studies confirmed its oncogenic roles in ccRCC. Further bioinformatic analysis and RNA immunoprecipitation revealed that PVT1 could function as an oncogenic transcript partly through sponging miR-200s to regulate BMI1, ZEB1 and ZEB2 expression. Besides, a novel splicing variant of PVT1 lacking exon 4 (PVT1ΔE4) was found to have a higher expression in ccRCC and could also promote cell proliferation and invasion as the full-length transcript did. Besides, SRSF1 decreased the inclusion of exon 4 of full-length transcript and increased the relative expression of PVT1ΔE4 in ccRCC. Mechanistic investigations indicated that PVT1ΔE4 could also upregulate the expression of BMI1, ZEB1 and ZEB2 through interacting with miR-200s. Our study helps reveal new molecular events in ccRCC and provides promising diagnostic and therapeutic targets for this disease.

Long non-coding RNA (lncRNAs) play a critical role in the development of cancers. LncRNA metastasis-associated lung adenocarcinoma transcript 1(MALAT1) has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer, bladder cancer and so on. Here, we found that MALAT1 exist a higher fold change (Tumor/Normal) in clear cell kidney carcinoma (KIRC) from The Cancer Genome Atlas (TCGA) Data Portal and a negative correlation with miR-200s family. We further demonstrated MALAT1 promote KIRC proliferation and metastasis through sponging miR-200s in vitro and in vivo. In addition, miR-200c can partly reverse the MALAT1's stimulation on proliferation and metastasis in KIRC. In summary we unveil a branch of the MALAT1/miR-200s/ZEB2 pathway that regulates the progression of KIRC. The inhibition of MALAT1 expression may be a promising strategy for KIRC therapy.