SREBP1 promotes invasive phenotypes by upregulating CYR61/CTGF via the Hippo-YAP pathway

Aberrant lipid metabolism provides bioenergetic, biosynthetic, and redox supplies to cancer cells. Previous studies have reported differential lipid profiling in thyroid malignancies. Sterol regulatory element-binding protein 1 (SREBP1), encoded by the SREBF1 gene, is a master regulator of cellular lipid homeostasis. The clinical and functional significance of SREBP1 in thyroid cancer is not well understood. Here, we showed that SREBP1 expression is significantly upregulated in invasive thyroid cancer than in normal thyroid tissue or benign thyroid nodules. High tumoral SREBP1 expression was associated with extrathyroidal extension, advanced disease stage, and shorter disease-specific survival in patients with differentiated thyroid cancer. SREBP1 overexpression significantly increased the oxygen consumption rate, filopodia formation, and migratory and invasive capacities of thyroid cancer cells. Knockdown of SREBF1 or treatment with an SREBP1 activation inhibitor fatostatin had the opposite effect. RNA-Seq analysis showed that modulation of SREBP1 expression was accompanied by corresponding changes in the expression of epithelial-mesenchymal transition markers and CYR61/CTGF. SREBP1-facilitated cell invasion could be abrogated by treatment with a YAP inhibitor such as verteporfin or genetic silencing of CYR61 or CTGF. In summary, SREBP1 upregulation can be used as a prognostic indicator for thyroid cancer, and SREBP1 overexpression is involved in cancer invasiveness, at least partly, through upregulation of CYR61/CTGF via the Hippo-YAP pathway.

Download Full-text

Phospholipase C Delta 3 inhibits apoptosis and promotes proliferation, migration, and invasion of thyroid cancer cells via Hippo pathway

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmab016 ◽

2021 ◽

Vol 53 (4) ◽

pp. 481-491

Author(s):

Lizhi Lin ◽

Jialiang Wen ◽

Bangyi Lin ◽

Hao Chen ◽

Adheesh Bhandari ◽

...

Keyword(s):

Thyroid Cancer ◽

Phospholipase C ◽

Cell Lines ◽

Epithelial Mesenchymal Transition ◽

Hippo Pathway ◽

Suppressive Effect ◽

The Cancer Genome Atlas ◽

Disease Stage ◽

Migration And Invasion ◽

Mesenchymal Transition

Abstract In recent decades, the incidence of thyroid cancer (TC) has rapidly increased, leading us to explore the complex underlying mechanisms. We identified the gene Phospholipase C Delta 3 (PLCD3) as a potential oncogene in TC by conducting the whole transcriptome sequencing. Our study is to understand the oncogenic role of PLCD3 in TC. We verified the overexpression of PLCD3 in TC from The Cancer Genome Atlas, Gene Expression Omnibus databases, and a locally validated cohort. Clinical correlation analysis showed that PLCD3 expression was related to histological type, T stage, lymph node metastasis (LNM), and disease stage. The high expression of PLCD3 could be a distinguishing factor for TC and its LNM. The biological function was examined using small interfering RNA-transfected TC cell lines. Silenced PLCD3 could inhibit colony formation, migration, and invasion ability and promote apoptosis of TC cell lines. PLCD3 silencing reversed the epithelial-mesenchymal transition but induced the apoptotic progress. Further exploration revealed that PLCD3 might be associated with critical genes of the Hippo pathway. The expressions of RHOA, YAP1/TAZ, and their downstream targets were decreased significantly when PLCD3 was down-regulated. YAP1 overexpression rescued the tumor-suppressive effect caused by PLCD3 silencing. This study demonstrates that PLCD3 is an oncogene that supports tumorigenesis and progression in TC, and PLCD3 may be a potential target gene for TC treatment.

Download Full-text

miR-32-5p Inhibits the Proliferation, Migration and Invasion of Thyroid Cancer Cells by Regulating Twist1

10.21203/rs.3.rs-552882/v1 ◽

2021 ◽

Author(s):

Qing Liu ◽

Ouyang Li ◽

Chi Zhou ◽

Yu Wang ◽

Chunxue He ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Transition Process ◽

Underlying Mechanism ◽

Luciferase Assay ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Thyroid Cancer Cells

Abstract Background: Thyroid cancer is the most prevalent malignancy and one of the leading causes of cancer-related deaths. Recent studies have revealed that microRNAs (miRNAs) play an important role in tumorigenesis in various cancer types by affecting the expression of its targets. However, the role of miR-32-5p in thyroid cancer remains limited. Methods: In this study, we attempt to explore the role of miR-32-5p in thyroid cancer and elucidate the underlying mechanism. Expression of miR-32-5p was determined by quantitative reverse transcription PCR. Functional assays were performed by CCK-8 assay, cell colony assay, cell apoptosis assay, cell migration and invasion assays, cell cycle assay and luciferase assay. Protein expression was analyzed by Western blot.Results: In the present study, the role of miR-32-5p in thyroid cancer was firstly explored. It is found that miR-32-5p was downregulated in thyroid cancer tissues and cells. Overexpression of miR-32-5p inhibited thyroid cancer cells proliferation, migration, invasion and epithelial‐mesenchymal transition process; while suppression of miR-32-5p exhibited an opposite effect on thyroid cancer cells. In addition, In addition, a luciferase assay showed Twist1 was identified as a direct target of miR-32-5p in thyroid cancer, and further study showed that restoration of Twist1 attenuated the biological effect of miR-32-5p on thyroid cancer cells. Conclusion: In conclusion, our results demonstrated miR-32-5p functions as a tumor suppressor by targeting Twist1 in thyroid cancer, providing a novel insight into thyroid cancer therapy.

Download Full-text