Dataset Information

ZEB1-AS1/miR-133a-3p/LPAR3/EGFR axis promotes the progression of thyroid cancer by regulating PI3K/AKT/mTOR pathway.

ABSTRACT: Background:Thyroid cancer (TC) is a member of common malignant tumors in endocrine system. To develop effective treatment, further comprehension of understanding molecular mechanism in TC is necessary. In this research, we attempted to search the underlying molecular mechanism in TC. Methods:ZEB1-AS1 expression was analyzed via qRT-PCR analysis. CCK-8, colony formation, flow cytometry and TUNEL assays were used to evaluate TC cell growth. The interaction between miR-133a-3p and LPAR3, EGFR and ZEB1-AS1 was testified through using RNA pull down and luciferase reporter assays. Results:LPAR3 and EGFR were expressed at high levels in TC tissues and cell lines. Besides, both LPAR3 and EGFR could promote TC cell growth. Later, miR-133a-3p was searched as an upstream gene of LPAR3 and EGFR, and LPAR3 could partially rescue the suppressive effect of miR-133a-3p overexpression on TC progression, whereas the co-transfection of LPAR3 and EGFR completely restored the inhibition. Next, ZEB1-AS1 was confirmed as a sponge of miR-133a-3p. ZEB1-AS1 has a negative correlation with miR-133a-3p and a positive association with LPAR3 and EGFR through ceRNA analysis. Importantly, ZEB1-AS1 boosted the proliferation and suppressed the apoptosis in TC cells. Through restoration assays, we discovered that ZEB1-AS1 regulated LPAR3 and EGFR expression to mediate TC cell proliferation and apoptosis by sponging miR-133a-3p. Further investigation also indicated the oncogenic role of ZEB1-AS1 by mediating PI3K/AKT/mTOR pathway. Conclusions:ZEB1-AS1 could be an underlying biomarker in TC.

SUBMITTER: Xia W

PROVIDER: S-EPMC7103072 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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ZEB1-AS1/miR-133a-3p/LPAR3/EGFR axis promotes the progression of thyroid cancer by regulating PI3K/AKT/mTOR pathway.

Xia Wu W Jie Wen W

Cancer cell international 20200329

<h4>Background</h4>Thyroid cancer (TC) is a member of common malignant tumors in endocrine system. To develop effective treatment, further comprehension of understanding molecular mechanism in TC is necessary. In this research, we attempted to search the underlying molecular mechanism in TC.<h4>Methods</h4>ZEB1-AS1 expression was analyzed via qRT-PCR analysis. CCK-8, colony formation, flow cytometry and TUNEL assays were used to evaluate TC cell growth. The interaction between miR-133a-3p and LP ...[more]

PMID: 32231464

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Project description:BackgroundBone metastasis is a leading cause of morbidity and mortality in advanced prostate cancer (PCa). Downexpression of miR-133a-3p has been found to contribute to the progression, recurrence and distant metastasis in PCa. However, clinical significance of miR-133a-3p in bone metastasis of PCa, and the biological role of miR-133a-3p and its molecular mechanisms underlying bone metastasis of PCa remain unclear.MethodsmiR-133a-3p expression was evaluated in 245 clinical PCa tissues by real-time PCR. Statistical analysis was performed to evaluate the clinical correlation between miR-133a-3p expression and clinicopathological features, and overall and bone metastasis-free survival in PCa patients. The biological roles of miR-133a-3p in the bone metastasis of PCa were investigated both in vitro and in vivo. Bioinformatics analysis, real-time PCR, western blot and luciferase reporter analysis were applied to demonstrate the relationship between miR-133a-3p and its potential targets. Western blotting and luciferase assays were examined to identify the underlying pathway involved in the anti-tumor role of miR-133a-3p. Clinical correlation of miR-133a-3p with its targets was verified in human PCa tissues.ResultsmiR-133a-3p expression is reduced in PCa tissues compared with the adjacent normal tissues and benign prostate lesion tissues, particularly in bone metastatic PCa tissues. Low expression of miR-133a-3p is significantly correlated with advanced clinicopathological characteristics and shorter bone metastasis-free survival in PCa patients by statistical analysis. Moreover, upregulating miR-133a-3p inhibits cancer stem cell-like phenotypes in vitro and in vivo, as well as attenuates anoikis resistance in vitro in PCa cells. Importantly, administration of agomir-133a-3p greatly suppresses the incidence of PCa bone metastasis in vivo. Our results further demonstrate that miR-133a-3p suppresses bone metastasis of PCa via inhibiting PI3K/AKT signaling by directly targeting multiple cytokine receptors, including EGFR, FGFR1, IGF1R and MET. The negative clinical correlation of miR-133a-3p with EGFR, FGFR1, IGF1R, MET and PI3K/AKT signaling activity is determined in clinical PCa tissues.ConclusionOur results unveil a novel mechanism by which miR-133a-3p inhibits bone metastasis of PCa, providing the evidence that miR-133a-3p may serve as a potential bone metastasis marker in PCa, and delivery of agomir-133a-3p may be an effective anti-bone metastasis therapeutic strategy in PCa.

Dataset Information

ZEB1-AS1/miR-133a-3p/LPAR3/EGFR axis promotes the progression of thyroid cancer by regulating PI3K/AKT/mTOR pathway.

Publications

ZEB1-AS1/miR-133a-3p/LPAR3/EGFR axis promotes the progression of thyroid cancer by regulating PI3K/AKT/mTOR pathway.

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