LncRNA PVT1: a Novel Therapeutic Target for Cancers

Huang

2020

Aging

We investigated the influence of the long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) on the malignant phenotype of non-small cell lung cancer (NSCLC) cells in vitro and in vivo. We also explored the mechanisms by which VPS9D1-AS1 exerts its oncogenic action during NSCLC progression. VPS9D1-AS1 expression was upregulated in NSCLC; the extent of its upregulation significantly correlated with patients' adverse clinicopathological characteristics and shorter overall survival. When VPS9D1-AS1 was knocked down in NSCLC cells, their proliferation, colony-forming capacity, migration, and invasiveness were lower, whereas their apoptosis rate was higher, compared to the control. VPS9D1-AS1 knockdown attenuated tumor growth of NSCLC cells in vivo. Mechanistically, VPS9D1-AS1 directly interacted with microRNA-532-3p (miR-532-3p) in NSCLC cells; the impact of VPS9D1-AS1 knockdown on NSCLC cells was attenuated by miR-532-3p inhibition. Furthermore, VPS9D1-AS1 knockdown decreased the expression of high mobility group AThook 2 (HMGA2) in NSCLC cells via miR-532-3p sponging. Recovery of HMGA2 expression partially reversed the inhibitory effects of VPS9D1-AS1 knockdown on NSCLC cells. Thus, VPS9D1-AS1 functions as a competing endogenous RNA that positively regulates HMGA2 expression by sponging miR-532-3p in NSCLC cells, suggesting that the VPS9D1-AS1-miR-532-3p-HMGA2 pathway can be a potential diagnostic and/or therapeutic target in NSCLC.

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA VPS9D1-AS1 augments the malignant phenotype of non-small cell lung cancer by sponging microRNA-532-3p and thereby enhancing HMGA2 expression

Huang

2020

Aging

“…The lncRNA PVT1 was confirmed to be associated with a variety of malignancies and promote tumor cell proliferation, migration, and tumor growth and metastasis . However, the role of PVT1 in other biological process, including the formation of adipose tissue, remained undefined.…”

Section: Introductionmentioning

confidence: 99%

The role and possible mechanism of long noncoding RNA PVT1 in modulating 3T3‐L1 preadipocyte proliferation and differentiation

Zhang

Qin

et al. 2020

IUBMB Life

Obesity is considered as a high‐risk susceptibility state for most metabolic disorders and is directly related to preadipocyte differentiation or adipogenesis. Long noncoding RNAs (lncRNAs) are the key factors which have regulatory functions on various critical physiological and biological processes. PVT1 was identified as an oncogenic lncRNA which could promote angiogenesis in gastric cancer. However, the functions and molecular pathways related to PVT1 in adipogenesis had not been clarified yet. In the current study, the purpose was to identify the effects of lncRNA PVT1 on adipogenesis and the relevant molecular processes. Quantitative real‐time polymerase chain reaction (RT‐qPCR) was used to quantify PVT1 expression. The mechanism for PVT1 to participate in 3T3‐L1 adipogenesis was identified by lentivirus‐mediated gain‐ and loss‐of‐function tests. The potential association of PVT1 with cell viability was checked by CCK‐8 assay and EdU staining. The gene expression for cytokines was determined by quantitative PCR (qPCR) and western blotting. PVT1 expression level was strongly upregulated after 3T3‐L1 preadipocytes differentiated. In mice, PVT1 was abundantly expressed in adipose tissue, and the obese mice had higher PVT1 expression in adipose tissue than that of nonobese mice. Predominantly, PVT1 was found inside the nuclei. Overexpressed PVT1 could promote 3T3‐L1 adipocyte differentiation as proved, which was the cause for the ability to accelerate lipid accumulation, by upregulating the expression of peroxisome proliferator activated receptor gamma, CCAAT/enhancer‐binding protein α, and adipocyte protein 2, while knockdown of PVT1 caused opposite effects. The RNA immunoprecipitation demonstrated the binding relationship between PVT1 and STAT3 suggesting the potential role of STAT3 in 3T3‐L1 preadipocyte differentiation. Furthermore, PVT1 could promote fatty acid synthesis but inhibit fatty acid oxidation. PVT1 was positively associated with 3T3‐L1 preadipocyte differentiation, which highlighted the potential of PVT1 as a therapeutic target for obesity treatment.

“…Furthermore, they can act as scaffold and decoy for miRNAs or proteins or can act as guides for proteins to influence gene transcription. lncRNAs were demonstrated to regulate cancer development and progression as either oncogenic or tumor-suppressive factors (Chi et al, 2019), and thus therapeutic concepts utilizing the key role of lncRNAs in cancer have emerged over the last decade (Pan et al, 2018b;Pichler et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Circulating Non-coding RNAs in Renal Cell Carcinoma—Pathogenesis and Potential Implications as Clinical Biomarkers

Barth

Drula

Ott

et al. 2020

Front. Cell Dev. Biol.

Liquid biopsy-the determination of circulating cells, proteins, DNA or RNA from biofluids through a "less invasive" approach-has emerged as a novel approach in all cancer entities. Circulating non-(protein) coding RNAs including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and YRNAs can be passively released by tissue or cell damage or actively secreted as cell-free circulating RNAs, bound to lipoproteins or carried by exosomes. In renal cell carcinoma (RCC), a growing body of evidence suggests circulating non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and YRNAs as promising and easily accessible blood-based biomarkers for the early diagnosis of RCC as well as for the prediction of prognosis and treatment response. In addition, circulating ncRNAs could also play a role in RCC pathogenesis and progression. This review gives an overview over the current study landscape of circulating ncRNAs and their involvement in RCC pathogenesis as well as their potential utility as future biomarkers in RCC diagnosis and treatment.