<p>Regulations of miR-183-5p and Snail-Mediated Shikonin-Reduced Epithelial-Mesenchymal Transition in Cervical Cancer Cells</p>

Abstract

Background: Shikonin, the main ingredient of Lithospermum erythrorhizon, has been reported to have antitumor effects via multiple targets and signaling pathways. However, the detailed mechanism underlying the effects in cervical cancer still remained unknown. Methods: MTT, wound-healing, transwell assays and flow cytometry experiments were used to measure cell growth, migration, invasion, and cell cycle analysis. Western blot was used to examine protein levels of Snail, Vimentin and E-cadherin. The expression level of miR-183-5p was measured via qRT-PCR. The E-cadherin promoter activity was detected via Secrete-PairTM Dual Luminescence Assay Kit. The transient transfection experiments were used for silencing of E-cadherin and overexpression of Snail genes. Tumor xenograft and bioluminescent imaging experiments were carried out to confirm the in vitro findings. Results: We showed that shikonin inhibited cell viability, migration and invasion, and induced cell cycle arrest in a dose-dependent manner in cervical cancer Hela and C33a cells. Mechanistically, we found that shikonin increased miR-183-5p expression and inhibited expression of transcription factor Snail protein. The mimics of miR-183-5p reduced, while the inhibitors of miR-183-5p reversed shikonin-inhibited Snail protein expression. In addition, shikonin decreased Vimentin, increased E-cadherin protein expressions and E-cadherin promoter activity, the latter was reversed in cells transfected with exogenous Snail overexpression vectors. Moreover, silencing of E-cadherin significantly abolished shikonin-inhibited cervical cancer cell growth. Similar findings were also observed in vivo using one xenograft mouse model. Conclusion: Our results show that shikonin inhibits EMT through inhibition of Snail and stimulation of miR-183-5p expressions, which resulted in induction of E-cadherin expression. Thus, blockade of EMT could be a novel mechanism underlying the anti-cervical cancer effects of shikonin.

Shikonin inhibits migration and invasion of triple-negative breast cancer cells by suppressing epithelial-mesenchymal transition via miR-17-5p/PTEN/Akt pathway

“…In consideration of the important role EMT played in cancer metastasis, we supposed whether the anti-metastasis effect of SHK was mediated by regulating the process of EMT. Therefore, in this study, we confirmed that TNBC cells acquired the epithelial phenotypes and lost the mesenchymal feature with the treatment of SHK, which was in accordance with the previous studies in cervical and lung cancers 18 , 19 .…”

“…SHK has been found to exert anti-cancer effects by inducing apoptosis and inhibiting proliferation, metastasis and drug resistance of cancer cells in various malignancies including breast cancer [15][16][17]. Of particular interest, it is reported that the EMT process might be a target of SHK in reducing metastasis in some cancers, such as cervical and lung cancer [18,19]. However, the effect of SHK on TNBC cells and its underlying mechanism is not fully understood.…”

Shikonin inhibits migration and invasion of triple-negative breast cancer cells by suppressing epithelial-mesenchymal transition via miR-17-5p/PTEN/Akt pathway

“…In consideration of the important role EMT played in cancer metastasis, we supposed whether the antimetastasis effect of SHK was mediated by regulating the process of EMT. Therefore, in this study, we confirmed that BC cells acquired the epithelial phenotypes and lost the mesenchymal feature with the treatment of SHK, which was in accordance with the previous studies in cervical and lung cancers [15,16].…”

“…SHK has been found to exert anti-cancer effects by inducing apoptosis and inhibiting proliferation, metastasis and drug resistance of cancer cells in various malignancies including breast cancer [12][13][14]. Of particular interest, it is reported that the EMT process might be a target of SHK in reducing metastasis in some cancers, such as cervical and lung cancer [15,16]. However, the effect of SHK on TNBC cells and its underlying mechanism is not fully understood.…”

Anti-Tumor Mechanisms Associated With Regulation of Non-Coding RNA by Active Ingredients of Chinese Medicine: A Review

“…E-cadherin, the most common EMT protein, plays an important role in tumor invasion, and the loss of E-cadherin expression promotes tumor and EMT. In the cervical cancer cell lines HeLa and C33a, Shikonin inhibits EMT by inducing miR-183-5p expression via E-cadherin ( 61 ). Similarly, miR-17-5p expression was upregulated in triple-negative breast cancer.…”