1. Academic Validation
  2. Ultrasound-targeted microbubble destruction-mediated miR-144-5p overexpression enhances the anti-tumor effect of paclitaxel on thyroid carcinoma by targeting STON2

Ultrasound-targeted microbubble destruction-mediated miR-144-5p overexpression enhances the anti-tumor effect of paclitaxel on thyroid carcinoma by targeting STON2

  • Cell Cycle. 2022 May;21(10):1058-1076. doi: 10.1080/15384101.2022.2040778.
Xuefeng Chen 1 2 Xinyuan Zhang 2 Yangyang Qian 3 Enhui Xia 2 Yu Wang 4 Qi Zhou 1
Affiliations

Affiliations

  • 1 Ultrasound Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, China.
  • 2 Ultrasound Department Yancheng No. 1 People's Hospital, Yancheng City, China.
  • 3 General Surgery Department, Yancheng No. 1 People's Hospital, Yancheng City, China.
  • 4 Emergency Department, Yancheng No. 1 People's Hospital, Yancheng City, China.
Abstract

The effects of miR-144-5p and paclitaxel (PTX) on thyroid carcinoma were less explored. Thus, we investigated the effects of miR-144-5p and PTX on thyroid carcinoma. The expression and target gene of miR-144-5p in thyroid carcinoma were analyzed by bioinformatics, y qRT-PCR and dual-luciferase reporter assay. After the transfection mediated by ultrasound-targeted microbubble destruction (UTMD) or Liposome, or the treatment of PTX, the viability, proliferation, migration, and invasion of thyroid carcinoma cells were detected by MTT, colony formation, wound-healing, and transwell assays. The expressions of miR-144-5p, STON2, MMP-9, E-cadherin, and N-Cadherin in cells were calculated via qRT-PCR or Western blotting. After a subcutaneous-xenotransplant tumor model was established using BALB/c nude mice and further treated with PTX and UTMD-mediated miR-144-5p, the volume, weight, and Ki67 level of tumor were recorded or evaluated by immunohistochemical assays. MiR-144-5p, which was low-expressed in thyroid carcinoma, directly down-regulated STON2 level. MiR-144-5p overexpression and PTX inhibited the viability, proliferation, migration, and invasion of thyroid carcinoma cells, while miR-144-5p silencing caused the opposite results. MiR-144-5p overexpression and PTX further up-regulated E-cadherin level and down-regulated those of MMP-9 and N-Cadherin in thyroid carcinoma cells. STON2 overexpression reversed the effects of miR-144-5p overexpression.. MiR-144-5p overexpression enhanced the inhibiting effect of PTX on tumor volume, weight, and Ki67 level of xenotransplant tumor, and the effects of UTMD-mediated miR-144-5p overexpression were stronger than those mediated by Liposome. Collectively, UTMD-mediated miR-144-5p overexpression enhanced the anti-tumor effect of PTX on thyroid carcinoma by targeting STON2.

Keywords

STON2; Thyroid carcinoma; miR-144-5p; paclitaxel; ultrasound-targeted microbubble destruction.

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