scholarly journals Long Noncoding RNA CCAL Promotes Papillary Thyroid Cancer Progression by Activation of NOTCH1 Pathway

Author(s):  
Ying Ye ◽  
Yanan Song ◽  
Juhua Zhuang ◽  
Saifei He ◽  
Jing Ni ◽  
...  

Long noncoding RNA CCAL has been reported to promote tumor progression in various human cancers, including hepatocellular carcinoma, osteosarcoma, and colorectal cancer. However, the role of CCAL in papillary thyroid cancer remains largely unknown. In the present study, we found that the expression of CCAL was upregulated in papillary thyroid tumor tissues compared to adjacent normal tissues. Moreover, the expression of CCAL was positively related with papillary thyroid cancer severity and TNM stage and predicated poor prognosis. Besides, we found that knockdown of CCAL significantly inhibited papillary thyroid cancer cell proliferation, migration, and invasion in vitro and reduced tumor growth and metastasis in vivo. We found that knockdown of CCAL dramatically decreased the expression of NOTCH1 and suppressed the activation of the NOTCH1 signaling pathway. Furthermore, overexpression of NOTCH1 rescued the proliferation, migration, and invasion in papillary thyroid cancer cells. Taken together, our data indicated that CCAL promoted papillary thyroid cancer development and progression by activation of the NOTCH1 pathway, which provided a new insight on the design of therapeutic targets.

Author(s):  
Xinyang Lu ◽  
Zhiqiang Liu ◽  
Xiaofei Ning ◽  
Lunhua Huang ◽  
Biao Jiang

The long noncoding RNA HOX transcript antisense RNA (HOTAIR) has been found to be overexpressed in many human malignancies and involved in tumor progression and metastasis. Although the downstream target through which HOTAIR modulates tumor metastasis is not well known, evidence suggests that microRNA-197 (miR-197) might be involved in this event. In the present study, the significance of HOTAIR and miR-197 in the progression of colorectal cancer was detected in vitro and in vivo. We found that HOTAIR expression was significantly increased in colorectal cancer cells and tissues. In contrast, the expression of miR-197 was obviously decreased. We further demonstrated that HOTAIR knockdown promoted apoptosis and inhibited cell proliferation, migration, and invasion in vitro and in vivo. Moreover, HOTAIR modulated the progression of colorectal cancer by competitively binding miR-197. Taken together, our study has identified a novel pathway through which HOTAIR exerts its oncogenic role and provided a molecular basis for potential applications of HOTAIR in the prognosis and treatment of colorectal cancer.


2021 ◽  
Author(s):  
Luyao Wu ◽  
Yu Ding ◽  
Xi Zhuang ◽  
Jingsheng Cai ◽  
Houchao Tong ◽  
...  

Abstract Background: Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological functions and the molecular mechanism of lncRNA FER1L4 in PTC.Methods: The expression of FER1L4 in PTC was determined via operating RT-PCR assays. Meanwhile, the clinical significance of FER1L4 in PTC patients was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and CDH4. Results: Upregulated expression of FER1L4 in PTC tissues was correlated with higher lymph node metastasis rate (p=0.020), extrathyroidal extension (p=0.013), and advanced TNM stage (p=0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene Cadherin 4 (CDH4). This condition was further confirmed in the rescue assays.Conclusions: This study firstly demonstrates FER1L4 plays an oncogenic role in PTC via FER1L4-miR-612-CDH4 axis and may provide a new therapeutic and diagnostic target for PTC.


2018 ◽  
Vol 233 (10) ◽  
pp. 6638-6648 ◽  
Author(s):  
Hong Zhang ◽  
Yuechang Cai ◽  
Li Zheng ◽  
Zhanlei Zhang ◽  
Xiaofeng Lin ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Junjie Chu ◽  
Li Tao ◽  
Teng Yao ◽  
Zizheng Chen ◽  
Xiaoxiao Lu ◽  
...  

AbstractPapillary thyroid cancer (PTC) has a continuously increasing incidence and imposes a heavy medical burden to individuals and society due to its high proportion of lymph node metastasis and recurrence in recent years. Circular RNAs, a class of noncoding RNAs, participate in the progression of many cancers, but the role of circRNAs in PTC is still rarely reported. In this study, circRNA deep sequencing was performed to identify differentially expressed circRNAs in PTC. CircRUNX1 was selected for its high expression in PTC, and circRUNX1 silencing was directly associated with the week potential for migration, invasion and proliferation of PTC in vivo and in vitro. Fluorescence in situ hybridization (FISH) was further used to confirm the cytoplasmic localization of circRUNX1, indicating the possible function of circRUNX1 as a ceRNAs in PTC progression through miRNA binding. MiR-296-3p was then confirmed to be regulated by circRUNX1 and to target DDHD domain containing 2 (DDHD2) by luciferase reporter assays. The strong antitumor effect of miR-296-3p and the tumor-promoting effect of DDHD2 were further investigated in PTC, indicating that circRUNX1 modulates PTC progression through the miR-296-3p/DDHD2 pathway. Overall, circRUNX1 plays an oncogenic role in PTC and provides a potentially effective therapeutic strategy for PTC progression.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Bin Zhou ◽  
Yugang Ge ◽  
Qing Shao ◽  
Liyi Yang ◽  
Xin Chen ◽  
...  

AbstractAccumulating evidence has suggested that long noncoding RNAs (lncRNAs) exert crucial modulation roles in the biological behaviors of multiple malignancies. Nonetheless, the specific function of lncRNA LINC00284 in papillary thyroid cancer (PTC) remains not fully understood. The objective of this research was to explore the influence of LINC00284 in PTC and elucidate its potential mechanism. The Cancer Genome Atlas (TCGA), gene expression omnibus (GEO) datasets were used to analyze LINC00284 expression differences in thyroid cancer and normal samples, followed by the verification of qRT-PCR in our own PTC and adjacent non-tumor tissues. The impacts of LINC00284 on PTC cell growth were detected in vitro via CCK-8, colony formation, EdU assays, and in vivo via a xenograft tumor model. Bioinformatics analyses and biological experiments were conducted to illuminate the molecular mechanism. We found that LINC00284 expression was remarkably increased in PTC tissues and its overexpression was closely correlated with larger tumor size. In addition, silencing LINC00284 could effectively attenuate PTC cell proliferation, induce apoptosis and G1 arrest in vitro, as well as suppress tumorigenesis in mouse xenografts. Mechanistic investigations showed that LINC00284 acted as a competing endogenous RNA (ceRNA) for miR-3127-5p, thus resulting in the disinhibition of its endogenous target E2F7. In short, our findings indicated that LINC00284–miR-3127-5p–E2F7 axis exerted oncogenic properties in PTC and may offer a new promising target for the diagnosis and therapy of PTC.


2020 ◽  
Vol 69 (1) ◽  
pp. 66-74
Author(s):  
Su Dong ◽  
Shuai Xue ◽  
Yue Sun ◽  
Zhe Han ◽  
Lele Sun ◽  
...  

MicroRNA-363-3 p (miR-363–3 p) has been reported to play a crucial role in tumor development and progression, and function as a tumor suppressor in many types of cancer. In our previous studies, we found that miRNA-363–3 p inhibited papillary thyroid carcinoma (PTC) progression by targeting PIK3CA. Meanwhile, we found that NIN1/RPN12 binding protein 1 (NOB1) was significantly upregulated in thyroid carcinoma tissue and downregulation of NOB1 expression significantly inhibited cell proliferation, migration and invasion in PTC. However, the correlation of NOB1 and miR-363–3 p has not been investigated. Here, we performed bioinformatic analysis to explore miRNA targeting NOB1. We found that NOB1 was a target of miR-363–3 p and miR-363–3 p regulated NOB1 expression at the translational and transcriptional levels by targeting its 3’ untranslated region (3'-UTR). Further, we showed that miR-363–3 p inhibited tumor progression by targeting NOB1 in vitro and in vivo. We found that overexpression miR-363–3 p or silencing NOB1 significantly increased G0/G1-phase and decreased S-phase in the human papillary thyroid cells, which led to a significant delay in cell proliferation, indicating miR-363–3 p and NOB1 are crucial for human papillary thyroid cancer tumorigenesis. Collectively, our data unveil that miR-363–3 p negatively regulates NOB1 activity by reducing its stability. This study provides a new therapeutic target for regulation of NOB1 stability to modulate human papillary thyroid cancer progression.


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