RESUMEN
TM4SF1, a member of the transmembrane 4 superfamily, is crucial for both healthy and malignant human tissues. The significant function of TM4SF1 in the incidence and progression of cancer has been widely recognized in recent years. Although some achievements have been made in the study of TM4SF1, the effect of TM4SF1 on cancer stemness in hepatocellular carcinoma (HCC) and its molecular basis are yet to be reported. We found through abundant in vitro and in vivo experiments which the expression of TM4SF1 was positively correlated with the progression and cancer stemness of HCC. We identified the downstream protein MYH9 of TM4SF1 and its final regulatory target NOTCH pathway using bioinformatics analysis and protein mass spectrometry. We cultivated a Lenvatinib-resistant strain from HCC cells to examine the relationship between cancer stemness and tumor drug resistance. The study confirmed that TM4SF1 could regulate the NOTCH pathway by upregulating MYH9, thus promoting cancer stemness and Lenvatinib resistance in HCC. This study not only provided a new idea for the pathogenesis of HCC but also confirmed that TM4SF1 might become a new intervention point to improve the clinical efficacy of Lenvatinib in treating HCC.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Cadenas Pesadas de Miosina , Proteínas de Neoplasias , Receptores Notch , Humanos , Antígenos de Superficie/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Receptores Notch/metabolismoRESUMEN
As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic ß-catenin destruction complex (GSK-3ß and Axin), promotes the ubiquitination degradation of ß-catenin, and inhibits its nuclear transfer, thus, decreasing c-Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.
Asunto(s)
Carcinoma Hepatocelular , Endodesoxirribonucleasas/metabolismo , Neoplasias Hepáticas , beta Catenina/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Neoplasias Hepáticas/genética , Ubiquitina/metabolismo , Vía de Señalización WntRESUMEN
Primulina hochiensis var. ochroleuca, a new variety from a limestone hill of karst areas, Guangxi, China is described with color photographs. It resembles P. hochiensis var. hochiensis, P. hochiensis var. ovata and P. hochiensis var. rosulata, but can be easily distinguished by a combination of characteristics, especially by its corolla color. We found only one population with approx. 3000 mature individuals at the type locality. This variety is provisionally assessed as vulnerable [VU C1] using IUCN criteria.
