scholarly journals Long non-coding RNA Lnc-408 promotes invasion and metastasis of breast cancer cell by regulating LIMK1

Oncogene ◽  
2021 ◽  
Author(s):  
Yina Qiao ◽  
Ting Jin ◽  
Shengdong Guan ◽  
Shaojie Cheng ◽  
Siyang Wen ◽  
...  

AbstractInvasion and metastasis are the leading causes of death in patients with breast cancer (BC), and epithelial-mesenchymal transformation (EMT) plays an essential role in this process. Here, we found that Lnc-408, a novel long noncoding RNA (lncRNA), is significantly upregulated in BC cells undergoing EMT and in BC tumor with lymphatic metastases compared with those without lymphatic metastases. Lnc-408 can enhance BC invasion and metastasis by regulating the expression of LIMK1. Mechanistically, Lnc-408 serves as a sponge for miR-654-5p to relieve the suppression of miR-654-5p on its target LIMK1. Knockdown or knockout of Lnc-408 in invasive BC cells clearly decreased LIMK1 levels, and ectopic Lnc-408 in MCF-7 cells increased LIMK1 expression to promote cell invasion. Lnc-408-mediated enhancement of LIMK1 plays a key role in cytoskeletal stability and promotes invadopodium formation in BC cells via p-cofilin/F-actin. In addition, the increased LIMK1 also facilitates the expression of MMP2, ITGB1, and COL1A1 by phosphorylating CREB. In conclusion, our findings reveal that Lnc-408 promotes BC invasion and metastasis via the Lnc-408/miR-654-5p/LIMK1 axis, highlighting a novel promising target for the diagnosis and treatment of BC.

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.


2020 ◽  
Vol 26 (15) ◽  
pp. 1742-1748
Author(s):  
Chaoying Song ◽  
Jiali Zhang ◽  
Zongyao Zhao ◽  
Yuxia Yang ◽  
Di Meng ◽  
...  

Background: LncRNA DLEU1 participates in various biological processes, playing an indispensable role in the pathophysiology of human diseases, especially in tumorigenesis and other processes. Besides, it may represent a promising target for biotherapy in numerous tumors. The aim of this review was to reveal the pathophysiological functions and mechanisms of lncRNA DLEU1 in different types of cancer. Methods: LncRNA DLEU1 participates in various biological processes, playing an indispensable role in the pathophysiology of human diseases, especially in tumorigenesis and other processes. Besides, it may represent a promising target for biotherapy in numerous tumors. The aim of this review was to reveal the pathophysiological functions and mechanisms of lncRNA DLEU1 in different types of cancer. Results: DLEU1 is a novel cancer-associated lncRNA that has been proved to be abnormally elevated in various malignancies, containing osteosarcoma, glioma, glioblastoma multiforme, hepatocellular carcinoma, bladder cancer, cervical cancer, non-small cell lung cancer, pancreatic ductal adenocarcinoma, colorectal cancer, oral squamous cell carcinoma, endometrial cancer, gastric cancer, Burkitt lymphoma and ovarian carcinoma. Besides, lncRNA LDEU1 has been demonstrated involving in the procession of proliferation, migration, invasion and inhibition of apoptosis of cancer cells. Conclusion: Long non-coding RNA DLEU1 is likely to represent an available biomarker or a potential therapeutic target in multiple tumors.


Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1156
Author(s):  
Charlotte Orre ◽  
Xavier Dieu ◽  
Jordan Guillon ◽  
Naïg Gueguen ◽  
Seyedeh Tayebeh Ahmadpour ◽  
...  

Despite improvements in therapeutic strategies for treating breast cancers, tumor relapse and chemoresistance remain major issues in patient outcomes. Indeed, cancer cells display a metabolic plasticity allowing a quick adaptation to the tumoral microenvironment and to cellular stresses induced by chemotherapy. Recently, long non-coding RNA molecules (lncRNAs) have emerged as important regulators of cellular metabolic orientation. In the present study, we addressed the role of the long non-coding RNA molecule (lncRNA) SAMMSON on the metabolic reprogramming and chemoresistance of MCF-7 breast cancer cells resistant to doxorubicin (MCF-7dox). Our results showed an overexpression of SAMMSON in MCF-7dox compared to doxorubicin-sensitive cells (MCF-7). Silencing of SAMMSON expression by siRNA in MCF-7dox cells resulted in a metabolic rewiring with improvement of oxidative metabolism, decreased mitochondrial ROS production, increased mitochondrial replication, transcription and translation and an attenuation of chemoresistance. These results highlight the role of SAMMSON in the metabolic adaptations leading to the development of chemoresistance in breast cancer cells. Thus, targeting SAMMSON expression levels represents a promising therapeutic route to circumvent doxorubicin resistance in breast cancers.


2020 ◽  
Vol 26 ◽  
Author(s):  
Bei Wang ◽  
Wen Xu ◽  
Yuxuan Cai ◽  
Chong Guo ◽  
Gang Zhou ◽  
...  

Background: CASC15, one of long non-coding RNA, is involved in the regulation of many tumor biological processes, and is expected to become a new biological therapeutic target. This paper aims to elucidate the pathophysiological function of CASC15 in various tumors. Methods: The relationship between CASC15 and tumors was analyzed by searching references, and summarizes the specific pathophysiological mechanism of CASC15. Results: LncRNA CASC15 is closely related to tumor development, and has been shown to be abnormally high expressed in all kinds of tumors, including breast cancer, cervical cancer, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, colon cancer, colorectal cancer, cardiac hypertrophy, intrahepatic cholangiocarcinoma, leukemia, melanoma, tongue squamous cell carcinoma, nasopharyngeal carcinoma. However, CASC15 has been found to be downexpressed abnormally in ovarian cancer, glioma and neuroblastoma. Besides, it is identified that CASC15 can affect the proliferation, invasion and apoptosis of tumors. Conclusion: LncRNA CASC15 has the potential to become a new therapeutic target or marker for a variety of tumors.


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