scholarly journals The role of ceRNA-mediated diagnosis and therapy in hepatocellular carcinoma

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yi Shi ◽  
Ji-Bin Liu ◽  
Jing Deng ◽  
Da-Zhi Zou ◽  
Jian-Jun Wu ◽  
...  

AbstractHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide due to its high degree of malignancy, high incidence, and low survival rate. However, the underlying mechanisms of hepatocarcinogenesis remain unclear. Long non coding RNA (lncRNA) has been shown as a novel type of RNA. lncRNA by acting as ceRNA can participate in various biological processes of HCC cells, such as tumor cell proliferation, migration, invasion, apoptosis and drug resistance by regulating downstream target gene expression and cancer-related signaling pathways. Meanwhile, lncRNA can predict the efficacy of treatment strategies for HCC and serve as a potential target for the diagnosis and treatment of HCC. Therefore, lncRNA serving as ceRNA may become a vital candidate biomarker for clinical diagnosis and treatment. In this review, the epidemiology of HCC, including morbidity, mortality, regional distribution, risk factors, and current treatment advances, was briefly discussed, and some biological functions of lncRNA in HCC were summarized with emphasis on the molecular mechanism and clinical application of lncRNA-mediated ceRNA regulatory network in HCC. This paper can contribute to the better understanding of the mechanism of the influence of lncRNA-mediated ceRNA networks (ceRNETs) on HCC and provide directions and strategies for future studies.

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Yue Zhao ◽  
Yaqi Yu ◽  
Wenxiu Zhao ◽  
Song You ◽  
Min Feng ◽  
...  

Abstract Hepatocellular carcinoma (HCC) is correlated with a poor prognosis and high mortality worldwide. Neuronal pentraxin 1 (NPTX1) has been reported to play an oncogenic role in several types of tumors. However, its expression and function in HCC is not yet fully understood. In the present study, we aimed to investigate the clinicopathological significance of NPTX1 in HCC and the underlying mechanisms. We observed that the expression of NPTX1 was decreased significantly in HCC and was associated with tumor size and metastasis in patients. Gain-of-function approaches revealed that NPTX1 suppressed the growth ability of HCC cells and contributed to mitochondria- related apoptosis. Furthermore, mechanistic investigations showed that the AKT (AKT serine/threonine kinase) pathway can regulate the effects of NPTX1 in HCC cells. After blocking the AKT pathway, the action of NPTX1 was greatly increased. In summary, we demonstrated that NPTX1 inhibited growth and promoted apoptosis in HCC via an AKT-mediated signaling mechanism. These findings indicate that NPTX1 is a potential clinical therapeutic target.


2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Jie Liang ◽  
Shujuan Zhang ◽  
Wei Wang ◽  
Yan Xu ◽  
Atikan Kawuli ◽  
...  

Abstract Cervical cancer (CC) is ranked as the fourth most common cancer that occurs in women universally, which normally causes pain in the lower belly. Plenty of studies have stated that the expression of long non-coding RNAs (lncRNAs) is linked to the cellular development of many kinds of cancers. DSCAM-AS1 has been reported to act as an oncogene in other cancer types and the aim of our study was to uncover the function and regulatory mechanism of DSCAM-AS1 in CC. In this research, our findings presented that DSCAM-AS1 expression was up-regulated in CC cells. DSCAM-AS1 led to the development of CC by enhancing cell proliferation, migration and invasion ability. DSCAM-AS1 was verified to combine with miR-877-5p and down-regulate the expression of miR-877-5p. Results also showed that ATXN7L3 was a downstream target gene of miR-877-5p and it was unfavorably modulated by miR-877-5p. Enhanced expression of ATXN7L3 counterbalanced the DSCAM-AS1 knockdown effect on the progression of CC. This was the first time to analyze the underlying regulatory mechanism of the oncogenic DSCAM-AS1. Our findings clarified that DSCAM-AS1 played as an oncogenic lncRNA by targeting miR-877-5p/ATXN7L3 axis to promote CC progression, which may provide insights into the prevention of CC.


2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Shanyang He ◽  
Yunhe Zhao ◽  
Xiaoping Wang ◽  
Yalan Deng ◽  
Zhiyong Wan ◽  
...  

Long non-coding RNA small nucleolar RNA host gene 20 (SNHG20) has been demonstrated to play crucial regulatory roles in many types of cancer. However, the biological function of long ncRNA (lncRNA) SNHG20 in ovarian cancer is still unclear. In the present study, we found that lncRNA SNHG20 was significantly increased in ovarian cancer. In addition, lncRNA SNHG20 knockdown suppressed the ovarian cancer progression, whereas overexpression of SNHG20 showed the opposite effects. Moreover, our results also revealed that lncRNA SNHG20 knockdown inhibited Wnt/β-catenin signaling activity by suppressing β-catenin expression and reversing the downstream target gene expression. Taken together, lncRNA SNHG20 plays an pivotal role in ovarian cancer progression by regulating Wnt/β-catenin signaling.


2018 ◽  
Vol 38 (4) ◽  
Author(s):  
ZheXing Wang ◽  
LiMing Pan ◽  
HaiXiang Yu ◽  
Yue Wang

Gefitinib resistance is one of the major obstacles for the treatment of lung adenocarcinoma (LAD). The present study aimed to investigate the effects of the long non-coding RNA (lncRNA), small nucleolar RNA host gene 5SNHG5 on gefitinib resistance in LAD and explore the underlying mechanisms. The quantitative real-time PCR (qRT-PCR) results showed that SNHG5 expression was significantly down-regulated in LAD patients with acquired gefitinib resistance and gefitinib resistant LAD cell lines. SNHG5 overexpression sensitized gefitinib resistant LAD cells to gefitinib treatment, while knockdown of SNHG5 rendered gefitinib sensitive LAD cells to gefitinib treatment. Bioinformatics analysis showed that SNHG5 exerted its function through interaction with miR-377, which was further confirmed by luciferase reporter assay in 293T cells. Overexpression of SNHG5 suppressed the expression of miR-377, while the knockdown of SNHG5 increased the miR-377 expression. MiR-377 expression was significantly up-regulated in LAD specimens with acquired gefitinib resistance and was negatively correlated with SNHG5 expression. In addition, CASP1 was predicted as a downstream target of miR-377. Overexpression of miR-377 suppressed the expression of CASP1 in PC9 cells and knockdown of miR-377 increased the CASP1 expression in PC9GR cells. In vitro functional assay showed that knockdown of CASP1 in SNHG5-overexpressed PC9GR cells abolished their gefitinib resistance. Overall, the present study demonstrated, for the first time, that the SNHG5/miR-377/CASP1 axis functions as an important role in LAD cells gefitinib resistance and potentially contributes to the improvement of LAD diagnosis and therapy.


2020 ◽  
Author(s):  
Shihao Di ◽  
Die Lu ◽  
Chunni Chen ◽  
Tianshi Ma ◽  
Zigui Zou ◽  
...  

Abstract Objective Breast cancer is the most common cancer in Chinese women. A number of studies proposed that long non-coding RNA plays an essential role in the regulation of invasion and metastasis of various forms of malignancy, including lung cancer, gastric cancer and bladder cancer. In this study, a long non-coding RNA MAFG-AS1 was explored in detail to understand the significance in the etiology of breast cancer.Methods Quantitative reverse transcription PCR (qRT-PCR) was used to examine the expression level of LncRNA MAFG-AS1 in tissues and cell lines. The association of LncRNA MAFG-AS1 expression and the postoperative prognosis was analyzed by the Kaplan-Meier method and log-rank test. Cell proliferation was evaluated in vitro and in vivo . Transwell assays were performed to examine the cell migration. Cell cycle and apoptosis was evaluated by flowcytometry analysis. The downstream target gene STC2 of LncRNA MAFG-AS1 was screened using the microarray analysis, which was validated by qRT-PCR, functional analysis, and rescue experiment.Results Expression of LncRNA MAFG-AS1 in the breast cancer tissues was significantly higher than the precancerous lesions. Elevated expression level of LncRNA MAFG-AS1 was correlated to the larger GTV (gross tumor volume), negative expression of ER, PR, Her2, lymph node metastasis, and poor prognosis. The potency of breast cancer proliferation, invasion and metastasis was inhibited in the absence of LncRNA MAFG-AS1.Tumorigenic capacity of breast cancer cells was inhibited in the absence of LncRNA MAFG-AS1. The downstream target gene regulated by LncRNA MAFG-AS1 was screened out by gene chip technology, GO analysis and QRT-PCR ultimately. Disrupted STC2 suppressed the cell proliferation and metastasis when the level of LncRNA MAFG-AS1 elevated.Conclusion The LncRNA MAFG-AS1 triggers tumorigenesis in the breast cancer and regulates breast cancer proliferation and metastasis by modulating the downstream target gene STC2. Results from our study indicates that LncRNA MAFG-AS1 can be used.


2019 ◽  
Vol 64 (5) ◽  
pp. 58-68
Author(s):  
Андрей Бушманов ◽  
Andrey Bushmanov ◽  
О. Клементьева ◽  
O. Klement'eva ◽  
А. Лабушкина ◽  
...  

In the presented review of publications, together with a brief analysis of the incidence, risk factors for the occurrence and methods of diagnosis of hepatocellular carcinoma (HCC), current problems and prospects for the application of nuclear medicine methods in the diagnosis and treatment of this disease are indicated. Hepatocellular carcinoma is one of the most common malignant tumors of the liver and is characterized by a rapidly progressing course with an unfavorable life expectancy. A variety of clinical manifestations of the disease creates certain difficulties in the early diagnosis of HCC. Although HCC screening is most commonly used to determine the level of alpha-fetoprotein (AFP), ultrasound (US), bolus CT and MRI, experience in the use of radionuclide imaging diagnostics, including positron emission tomography, is important in clinical practice (PET), which, not being the main method of primary diagnosis of HCC, however, confirmed their relevance in the differential diagnosis between a benign tumor and metastasis with unclear diagnostic data, as well as in the process of monitoring treatment and in the diagnosis of distant metastases. Conceptual issues in determining the treatment strategy of patients with HCC, depending on the staging of the disease, the prospects for optimizing treatment strategies and traditional methods of treating HCC in detail and in depth are covered in various publications, including publications of domestic authors. Based on this, the authors of the article limited themselves to a brief analysis of the use of embolization and radiation therapy methods for treating HCC, the active development of which in the last decade, as well as promising early results of treatment, suggest that radiation therapy can be considered as the main treatment method for HCC traditional methods. Further study and development of radionuclide methods for the diagnosis and therapy of HCC, as well as the search and study of new radiopharmaceuticals for diagnosis and regional intraarterial radiotherapy is one of the promising directions in modern approaches to the diagnosis and treatment of HCC.


2020 ◽  
Vol 8 (7) ◽  
pp. 232596712093210
Author(s):  
Michael T. Freehill ◽  
Sandeep Mannava ◽  
Laurence D. Higgins ◽  
Alexandre Lädermann ◽  
Austin V. Stone

Background: A variety of thrower’s exostoses are grouped under the term Bennett lesion, which makes understanding diagnosis and treatment difficult. Purpose: To identify all types of reported thrower’s and overhead athlete’s exostoses and categorize them into a classification system to allow a morphology-based classification. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of all articles pertaining to Bennett lesions and thrower’s exostosis was performed. The classification and treatments were evaluated to describe the types, proposed causes, diagnosis, and treatment options. Results: A total of 27 studies were included in the systematic review. The anatomic locations referenced in the study demonstrated posteroinferior, posterior, and posterosuperior glenoid lesions. Aggregate radiographic data demonstrated 158 of 306 patients (52%) with a thrower’s exostosis of any type and location. Of these 158 patients with a radiographic lesion, 119 (75%) patients were symptomatic. The locations were posteroinferior in 110 patients (70%), directly posterior in 2 patients (1.3%), posterosuperior in 44 patients (28%), and unknown in 2 patients (1.3%). Avulsed lesions were present in 9 (5.7%) posteroinferior lesions, 0 direct posterior lesions, and 2 (1.3%) posterosuperior lesions. Treatment plans included both nonoperative and operative strategies, but operative intervention was more commonly reported for detached lesions. After operative intervention, only 61% of reported athletes returned to preinjury performance. Conclusion: Based on a comprehensive review of the literature, we identified several anatomic locations for a thrower’s exostosis beyond the classic Bennett lesion. We categorized the reported exostoses into a new classification system for description of location and type (subperiosteal or free fragment) of the thrower’s exostosis, which may be used to study future treatments. Current treatment strategies recommend that surgical treatment of thrower’s exostosis is considered only after exhausting nonoperative management because reported return to sport is variable after surgery. The effectiveness of excision or repair for both subperiosteal and detached lesions has not been established.


2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Shuaishuai Zhuo ◽  
Miaomiao Sun ◽  
Rumeng Bai ◽  
Die Lu ◽  
Shihao Di ◽  
...  

AbstractGastric cancer (GC) is one of the most common malignancies worldwide, but its molecular mechanisms remain unclear. Increasing evidence indicates that long non-coding RNAs (LncRNAs) play a pivotal role in various cancers recently. Our present study focused on exploring the function of long intergenic non-coding RNA 00473 (LINC00473) in GC. In this study, we found that LINC00473 expression was aberrantly increased in tumor tissues compared with the paired para-cancerous tissues. The expression of high LINC00473 in GC was notably correlated with a higher risk of lymphatic metastasis, a higher incidence of vascular cancer embolus, and advanced TNM stage. Further experiments showed that the overexpression of LINC00473 could promote the proliferation and metastasis of GC cells both in vitro and in vivo. The apoptosis of GC cells increased significantly by the decrease of LINC00473. Mechanistically, LINC00473 could sponge miR-16-5p in the cytoplasm and relieve its suppression of CCND2. Moreover, AQP3 was found to be a significant downstream target gene for LINC00473 through RNA transcriptome sequencing, as demonstrated by qRT-PCR and western blot. Overexpression of LINC00473 can partially reverse the effects of AQP3 decrease on GC proliferation and metastasis. LINC00473 regulated AQP3 expression through CREB was confirmed by western blot. Our research indicates that LINC00473/miR-16-5p/CCND2 axis plays a role in the proliferation of GC and modulates AQP3 to influence GC cell metastasis, making it a potential therapeutic target for GC.


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