LncRNA RP11-295G20.2 regulates hepatocellular carcinoma cell growth and autophagy by targeting PTEN to lysosomal degradation

AbstractPTEN is a crucial tumor suppressor and loss of PTEN protein is involved in various cancers. However, the detailed molecular mechanisms of PTEN loss in cancers remain elusive, especially the involvement of lncRNAs. Here, lncRNA RP11-295G20.2 is found to be significantly upregulated in hepatocellular carcinoma (HCC) and promotes the growth of liver cancer cells both in vitro and in vivo. Furthermore, RP11-295G20.2 inhibits autophagy in liver cancer cells. Interestingly, RP11-295G20.2 directly binds to the PTEN protein and leads to its degradation. RP11-295G20.2 expression is inversely correlated with PTEN protein expression in 82 TCGA/TCPA-LIHC samples. Surprisingly, RP11-295G20.2-induced PTEN degradation occurs through the lysosomal pathway instead of the proteasome pathway. RP11-295G20.2 binds to the N terminus of PTEN and facilitates the interaction of p62 with PTEN. Thus, PTEN is translocated into lysosomes and degraded. RP11-295G20.2 also influences AKT phosphorylation and forkhead box O 3a (FOXO3a) translocation into the nucleus, in turn regulating the transcription of autophagy-related genes. Collectively, RP11-295G20.2 directly binds to PTEN and enables its lysosomal degradation. This newly identified RP11-295G20.2/PTEN axis reveals an unexplored molecular mechanism regarding PTEN loss in liver cancer and might provide new therapeutic benefits for liver cancer patients.

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Estrogen signalling through amphiregulin may be implicated in human hepatocellular carcinoma

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci.2011.003 ◽

2011 ◽

Vol 5 (3) ◽

pp. 153-160 ◽

Cited By ~ 2

Author(s):

Giuseppe Carruba ◽

Vitale Miceli ◽

Letizia Cocciadiferro ◽

Maurizio Zarcone ◽

Biagio Agostara ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Cancer Cells ◽

Human Hepatocellular Carcinoma ◽

Mrna Levels ◽

Wild Type ◽

Liver Cancer Cells ◽

Huh7 Cells ◽

Liver Tissues

AbstractBackground:We investigated aromatase (Aro)-driven estrogen formation in non-tumoral and malignant liver tissues and cells, also in relation to expression of the estrogen receptors α and β (ERα and ERβ) and amphiregulin (AREG), aiming to gain insights into the potential role of estrogens in human hepatocellular carcinoma (HCC).Materials and methods:Chromatographic and reverse transcriptase polymerase chain reaction (RT-PCR) analyses were used to assess activity and expression of the Aro enzyme and AREG as well as the expression of wild-type and variant ERs, both in vivo and in vitro.Results:Following 24 h and 72 h incubation of liver tissues or cells with testosterone, human HCC tissues and HepG2 hepatoma cells showed elevated Aro activity (estrogen formation, respectively, of 20% and 52%–99%). By contrast, no Aro activity could be detected in non-tumoral tissues and HA22T liver cancer cells. Cirrhotic samples and Huh7 cells exhibited intermediate enzyme activity, with estrogen formation of 4% and 34%, respectively. Markedly lower or undetectable Aro mRNA levels were observed in HA22T cells and non-tumoral liver tissues compared with HepG2 cells and HCC samples. Cirrhotic specimens displayed variable transcript levels. Interestingly, no or low expression of wild-type ERα and ERβ could be observed in liver cancer cells and malignant tissues. However, ubiquitous expression of the hERα46 variant and occasional expression of the hERβ2/Cx variant were observed in cancer tissues and cells.Conclusions:It is noteworthy that the pattern of wild-type ERα was inversely related to Aro, whilst AREG expression was consistently associated with that of Aro. This combined evidence suggests that locally elevated Aro activity may increase malignant cell proliferation also through AREG signalling.

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In vitro study of doxorubicin-loaded thermo- and pH-tunable carriers for targeted drug delivery to liver cancer cells

Journal of Industrial and Engineering Chemistry ◽

10.1016/j.jiec.2021.08.012 ◽

2021 ◽

Vol 104 ◽

pp. 93-105

Author(s):

Sikhumbuzo Charles Kunene ◽

Kuen-Song Lin ◽

Meng-Tzu Weng ◽

Maria Janina Carrera Espinoza ◽

Chun-Ming Wu

Keyword(s):

Drug Delivery ◽

Liver Cancer ◽

Cancer Cells ◽

Targeted Drug Delivery ◽

In Vitro Study ◽

Vitro Study ◽

Liver Cancer Cells ◽

Targeted Drug

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Aggregation-Induced Emission (AIE) Fluorophore Exhibits a Highly Ratiometric Fluorescent Response to Zn2+ in vitro and in Human Liver Cancer Cells

Chemistry - A European Journal ◽

10.1002/chem.201701948 ◽

2017 ◽

Vol 23 (53) ◽

pp. 13067-13075 ◽

Cited By ~ 16

Author(s):

Hassan Mehdi ◽

Weitao Gong ◽

Huimin Guo ◽

Michael Watkinson ◽

Hua Ma ◽

...

Keyword(s):

Liver Cancer ◽

Cancer Cells ◽

Human Liver ◽

Aggregation Induced Emission ◽

Liver Cancer Cells ◽

Fluorescent Response ◽

Human Liver Cancer ◽

Human Liver Cancer Cells

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Synergistic Interaction between the HDAC Inhibitor, MPT0E028, and Sorafenib in Liver Cancer Cells In Vitro and In Vivo

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-12-3909 ◽

2014 ◽

Vol 20 (5) ◽

pp. 1274-1287 ◽

Cited By ~ 31

Author(s):

Chun-Han Chen ◽

Mei-Chuan Chen ◽

Jing-Chi Wang ◽

An-Chi Tsai ◽

Ching-Shih Chen ◽

...

Keyword(s):

Liver Cancer ◽

Cancer Cells ◽

Hdac Inhibitor ◽

Synergistic Interaction ◽

Liver Cancer Cells

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A homeopathic nosode, Hepatitis C 30 demonstrates anticancer effect against liver cancer cells in vitro by modulating telomerase and topoisomerase II activities as also by promoting apoptosis via intrinsic mitochondrial pathway

Journal of Integrative Medicine ◽

10.1016/s2095-4964(16)60251-0 ◽

2016 ◽

Vol 14 (3) ◽

pp. 209-218 ◽

Cited By ~ 7

Author(s):

Jesmin Mondal ◽

Jayeeta Das ◽

Rajesh Shah ◽

Anisur Rahman Khuda-Bukhsh

Keyword(s):

Hepatitis C ◽

Liver Cancer ◽

Cancer Cells ◽

Topoisomerase Ii ◽

Mitochondrial Pathway ◽

Anticancer Effect ◽

Liver Cancer Cells ◽

C 30

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The interaction of bacterial magnetosomes and human liver cancer cells in vitro

Journal of Magnetism and Magnetic Materials ◽

10.1016/j.jmmm.2016.10.106 ◽

2017 ◽

Vol 427 ◽

pp. 105-110 ◽

Cited By ~ 6

Author(s):

Pingping Wang ◽

Chuanfang Chen ◽

Changyou Chen ◽

Yue Li ◽

Weidong Pan ◽

...

Keyword(s):

Liver Cancer ◽

Cancer Cells ◽

Human Liver ◽

Liver Cancer Cells ◽

Human Liver Cancer ◽

Human Liver Cancer Cells

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In Vitro Experiments of Microwave Ablation in Liver Cancer Cells (Effects of Microwave Power and Heating Time)

2020 IEEE 7th International Conference on Industrial Engineering and Applications (ICIEA) ◽

10.1109/iciea49774.2020.9102010 ◽

2020 ◽

Author(s):

Purachet Manop ◽

Pornthip Keangin ◽

Norased Nasongkla ◽

Komgrit Eawsakul

Keyword(s):

Liver Cancer ◽

Cancer Cells ◽

Microwave Power ◽

Microwave Ablation ◽

Heating Time ◽

In Vitro Experiments ◽

Liver Cancer Cells

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Downexpression of HSD17B6 correlates with clinical prognosis and tumor immune infiltrates in hepatocellular carcinoma

Cancer Cell International ◽

10.1186/s12935-020-01298-5 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Lei Lv ◽

Yujia Zhao ◽

Qinqin Wei ◽

Ye Zhao ◽

Qiyi Yi

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Immune Responses ◽

Cancer Cells ◽

Negative Regulator ◽

Functional Enrichment ◽

Migration And Invasion ◽

Relative Reduction ◽

Clinical Prognosis ◽

Liver Cancer Cells

Abstract Background Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6), a key protein involved in synthetizing dihydrotestosterone, is abundant in the liver. Previous studies have suggested a role for dihydrotestosterone in modulating progress of various malignancies, and HSD17B6 dysfunction was associated with lung cancer and prostate cancer. However, little is known about the detailed role of HSD17B6 in hepatocellular carcinoma (HCC). Methods Clinical implication and survival data related to HSD17B6 expression in patients with HCC were obtained through TCGA, ICGC, ONCOMINE, GEO and HPA databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The ChIP-seq data were obtained from Cistrome DB. Protein–Protein Interaction and gene functional enrichment analyses were performed in STRING database. The correlations between HSD17B6 and tumor immune infiltrates was investigated via TIMER and xCell. The proliferation, migration and invasion of liver cancer cells transfected with HSD17B6 were evaluated by the CCK8 assay, wound healing test and transwell assay respectively. Expression of HSD17B6, TGFB1 and PD-L1 were assessed by quantitative RT-PCR. Results HSD17B6 expression was lower in HCC compared to normal liver and correlated with tumor stage and grade. Lower expression of HSD17B6 was associated with worse OS, PFS, RFS and DSS in HCC patients. HNF4A bound to enhancer and promoter regions of HSD17B6 gene, activating its transcription, and DNA methylation of HSD17B6 promoter negatively controlled the expression. HSD17B6 and its interaction partners were involved in androgen metabolism and biosynthesis in liver. HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infiltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1. Conclusions This study indicate that HSD17B6 could be a new biomarker for the prognosis of HCC and an important negative regulator of immune responses in HCC.

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