MTA2 promotes HCC progression through repressing FRMD6, a key upstream component of hippo signaling pathway

Guan, Chengjian; Chang, Zhenyu; Gu, Xinjin; Liu, Rong

doi:10.1016/j.bbrc.2019.05.025

Cited by 14 publications

(25 citation statements)

References 35 publications

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“…20,21 MTA2 acts as a central hub for cytoskeletal organization and transcription and provides a link between nuclear and cytoskeletal organization. It was also found to be significantly upregulated and to function as an oncogene in a wide range of malignancies such as renal cancer, 22 hepatocellular carcinoma, 23 and pancreatic ductal adenocarcinoma. 24 Moreover, MTA2 expression is regulated at the posttransciptional level in gastric cancer, 25 and the long noncoding RNA HOTAIR promotes the invasion and metastasis of oral squamous cell carcinoma through targeting MTA2.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ-NCOR2 accelerates papillary thyroid cancer progression by sponging miR-516a-5p to upregulate metastasis-associated protein 2 expression

Luan

Wang

et al. 2020

J Int Med Res

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Objective Papillary thyroid cancer (PTC) is one of the most prevalent endocrine malignancies and the fifth most common cancer in women. Circular RNAs (circRNAs) have been shown to play vital functions in cancers, but few studies have focused on the functions and mechanism of dysregulated circRNAs in PTC. Methods Quantitative reverse transcription PCR was used to measure circ-NCOR2 levels in PTC tissues and cell lines. The functions of circ-NCOR2 in PTC were examined by analysis using the cell counting kit-8, clone forming, flow cytometry, and Transwell experiments. Bioinformatic analysis and dual luciferase reporter gene testing were used to identify the mechanisms of circ-NCOR2. Results Circ-NCOR2 overexpression was observed in PTC tissues and cells. Silenced or overexpressed expression of circ-NCOR2 strikingly attenuated or facilitated, respectively, the growth, migration, and invasion of PTC cells. Mechanistically, miR-615a-5p was identified as the target of circ-NCOR2. Moreover, circ-NCOR2 enhanced the expression of metastasis-associated protein 2 (MTA2) by sponging miR-615a-5p, thereby facilitating PTC cell progression. Conclusions Taken together, our findings reveal a novel circ-NCOR2/miR-615a-5p/MTA2 axis in PTC, which could become a potential therapeutic target for this disease.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circ-NCOR2 accelerates papillary thyroid cancer progression by sponging miR-516a-5p to upregulate metastasis-associated protein 2 expression

Luan

Wang

et al. 2020

J Int Med Res

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“…Moreover, miR-454-3p inhibitor reversed the downregulation of FRMD6 protein level induced by linc00887 knockdown. FRMD6 was reported to be a key upstream component of the Hippo signaling pathway [28,29], and Hippo signaling pathway is considered a key carcinogenic pathway for multiple tumors [28,30,31] or asthma treatment [32]. This Hippo pathway is one of the main conservative mechanisms controlling cell contact inhibition, organ size control and cancer development [33], and the downstream of the signaling pathway is transcriptional coactivator yorkie (Yki)/the transcriptional coactivator Yes-associated protein (YAP)/TAZ transcriptional activator [34].…”

Section: Discussionmentioning

confidence: 99%

Linc00887 suppresses tumorigenesis of cervical cancer through regulating the miR-454-3p/FRMD6-Hippo axis

Li¹,

Wang²,

Zhi

et al. 2021

Cancer Cell Int

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Background Emerging evidence suggested that long intergenic noncoding RNA (lincRNA) 00887 (NR_024480) reduced the invasion and metastasis of non-small cell lung cancer by sponging miRNAs degradation. However, the role and regulatory mechanism of linc00887 in the progression of cervical cancer remain largely unknown. Methods In vivo or vitro, RT-qPCR assay was used to detect the expression of linc00887 in human normal (N = 30), cervical cancer tissues (N = 30), human normal cervical epithelial cells (Ect1/E6E7) and cervical cancer cell lines (HeLa, C33A). Then, CCK-8 and Transwell assays were used to examine cell proliferation and invasion when linc00887 was overexpressed or knocked down. In addition, bioinformatics, luciferase reporter gene and pull-down assays were used to predict and validate the relationship between linc00887 and miR-454-3p. Moreover, we detected the expression of miR-454-3p in Ect1/E6E7, HeLa and C33A cells when linc00887 was overexpressed or knocked down. Cell proliferation and invasion were also measured when pcDNA-linc00887 and miR-454-3p were transfected alone or together. Next, miR-454-3p target gene was predicted and validated by bioinformatics and luciferase reporter gene assays. Gain- and loss-of-function experiments were performed in HeLa cells to evaluate the effect of miR-454-3p or linc00887 on the expression of FERM domain containing protein 6 (FRMD6) protein and several key proteins in the FRMD6-Hippo signaling pathway. Results Linc00887 was downregulated in cervical cancer tissues or human cervical cancer cell lines (Hela, C33A) compared with normal tissues or cell lines. Overexpression of linc00887 inhibited proliferation and invasion HeLa and C33A cells, while linc00887 knockdown had the opposite effect. Linc00887 bound with miR-454-3p, and overexpression of miR-454-3p rescued linc00887-induced inhibition proliferation and invasion of HeLa cells. MiR-454-3p targeted and suppressed the expression of FRMD6, and linc00887 suppressed tumorigenesis of cervical cancer through activating the FRMD6-Hippo signaling pathway. Conclusions Linc00887, sponging miR-454-3p, inhibited the progression of cervical cancer by activating the FRMD6-Hippo signaling pathway.

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“…Based on the data from GEPIA and our HCC samples from clinical patients, the major components (YAP and TAZ) in HIPPO pathway were closely associated with the FGF21 and IL-17A expression levels in regard to the prognosis. Accumulating evidence suggests that HIPPO pathway plays a critical role linking the NASH-HCC transition 54 - 56 . Further study is needed to address the accurate role of YAP and TAZ, which could be important carcinogenetic signaling involved in the NASH-HCC initiation and progression.…”

Section: Discussionmentioning

confidence: 99%

Lack of FGF21 promotes NASH-HCC transition via hepatocyte-TLR4-IL-17A signaling

et al. 2020

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Rationale: Hepatocellular carcinoma (HCC) has been increasingly recognized in nonalcoholic steatohepatitis (NASH) patients. Fibroblast growth factor 21 (FGF21) is reported to prevent NASH and delay HCC development. In this study, the effects of FGF21 on NASH progression and NASH-HCC transition and the potential mechanism(s) were investigated. Methods: NASH models and NASH-HCC models were established in FGF21Knockout (KO) mice to evaluate NASH-HCC transition. IL-17A signaling was investigated in the isolated hepatic parenchymal cells, splenocytes, and hepatocyte and HCC cell lines. Results: Lack of FGF21 caused significant up-regulation of the hepatocyte-derived IL-17A via Toll-like receptor 4 (TLR4) and NF-κB signaling. Restoration of FGF21 alleviated the high NAFLD activity score (NAS) and attenuated the TLR4-triggered hepatocyte-IL-17A expression. The HCC nodule number and tumor size were significantly alleviated by treatments of anti-IL-17A antibody. Conclusion: This study revealed a novel anti-inflammatory mechanism of FGF21 via inhibiting the hepatocyte-TLR4-IL-17A signaling in NASH-HCC models. The negative feedback loop on the hepatocyte-TLR4-IL-17A axis could be a potential anti-carcinogenetic mechanism for FGF21 to prevent NASH-HCC transition.

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MTA2 promotes HCC progression through repressing FRMD6, a key upstream component of hippo signaling pathway

Cited by 14 publications

References 35 publications

Circular RNA circ-NCOR2 accelerates papillary thyroid cancer progression by sponging miR-516a-5p to upregulate metastasis-associated protein 2 expression

Circular RNA circ-NCOR2 accelerates papillary thyroid cancer progression by sponging miR-516a-5p to upregulate metastasis-associated protein 2 expression

Linc00887 suppresses tumorigenesis of cervical cancer through regulating the miR-454-3p/FRMD6-Hippo axis

Lack of FGF21 promotes NASH-HCC transition via hepatocyte-TLR4-IL-17A signaling

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