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Silencing long non-coding RNA DLX6-AS1 or restoring microRNA-193b-3p enhances thyroid carcinoma cell autophagy and apoptosis via depressing HOXA1
Authors:Ling Feng  Ru Wang  Yifan Wang  Xixi Shen  Qian Shi  Meng Lian  Hongzhi Ma  Jugao Fang
Institution:1. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China

Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing, China

Contribution: Formal analysis (equal), Funding acquisition (equal), Resources (equal);2. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China

Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing, China

Contribution: ​Investigation (equal), Methodology (equal), Project administration (equal);3. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China

Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing, China

Contribution: Software (equal), Writing - original draft (equal), Writing - review & editing (equal);4. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China

Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing, China

Contribution: Validation (equal), Visualization (equal), Writing - original draft (equal);5. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China

Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing, China

Contribution: Funding acquisition (equal), Validation (equal), Writing - review & editing (equal);6. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China

Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing, China

Contribution: Funding acquisition (equal), Writing - original draft (equal);7. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China

Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing, China

Contribution: Conceptualization (equal), Funding acquisition (equal), Supervision (equal);8. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China

Abstract:Long non-coding RNA DLX6 antisense RNA 1 (DLX6-AS1) lists a critical position in thyroid carcinoma (TC) development. However, the overall comprehension about DLX6-AS1, microRNA (miR)-193b-3p and homeobox A1 (HOXA1) in TC is not thoroughly enough. Concerning to this, this work is pivoted on DLX6-AS1/miR-193b-3p/HOXA1 axis in TC cell growth and autophagy. TC tissues and adjacent normal thyroid tissues were collected, in which expression of DLX6-AS1, miR-193b-3p and HOXA1 was tested, together with their interactions. TC cells were transfected with DLX6-AS1/miR-193b-3p-related oligonucleotides or plasmids to test cell growth and autophagy. Tumorigenesis in nude mice was observed. DLX6-AS1 and HOXA1 were up-regulated, and miR-193b-3p was down-regulated in TC. Depleted DLX6-AS1 or restored miR-193b-3p disturbed cell growth and promoted autophagy. DLX6-AS1 targeted miR-193b-3p and positively regulated HOXA1. miR-193b-3p inhibition mitigated the impaired tumorigenesis induced by down-regulated DLX6-AS1. Tumorigenesis in nude mice was consistent with that in cells. It is clear that DLX6-AS1 depletion hinders TC cell growth and promotes autophagy via up-regulating miR-193b-3p and down-regulating HOXA1.
Keywords:autophagy  HOXA1  long non-coding RNA DLX6-AS1  metastasis  microRNA-193b-3p  thyroid carcinoma
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