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LncRNA HAGLR May Aggravate Melanoma Malignancy Via miR-4644/ASB11 Pathway

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Abstract

In this study, we aimed to assess the biological functions of HAGLR and its underlying mechanisms in melanoma. HAGLR and ASB11 were knocked down by transfection with the corresponding siRNAs. Meanwhile, miR-4644 was downregulated using the miR-4644 inhibitor treatment. The target interactions among the three molecules were demonstrated using dual-luciferase reporter and RNA immunoprecipitation assays. The levels of HAGLR, miR-4644, and ASB11 in melanoma cells and tissues were assessed using quantitative real‑time PCR and western blotting. The functions and mechanisms underlying HAGLR action in melanoma progression were examined using Cell Counting Kit-8, Transwell, Caspase-3 activity, and xenograft tumor formation assays. HAGLR and ASB11 expression were elevated, whereas that of miR-4644 was downregulated in melanoma cells and tissues. The viability and migration of melanoma cells (A875 and A375) were markedly suppressed by the knockdown of HAGLR and ASB11 but promoted following miR-4644 inhibitor transfection. In contrast, apoptosis showed the opposite trend. In vivo, tumor weight declined considerably with downregulation of HAGLR. Mechanistically, HAGLR sponges miR-4644, increasing the levels of ASB11 and further aggravating melanoma. It latter negatively targets ASB11 in melanoma cells. Hence, the HAGLR-miR-4644-ASB11 axis may be a promising target for melanoma treatment.

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Author notes

  1. Longjun Luo and Wenhui Zhang have contributed equally to this work.

Authors and Affiliations

  1. Department of Burns & Skin Wounds Repair Center, The Third Hospital of Wuhan, Wuhan, 430070, Hubei, People’s Republic of China

    Longjun Luo

  2. Department of Plastic & Cosmetic Surgery, Tongji Medical College Hospital, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China

    Wenhui Zhang

  3. Department of Orthopedics & Plastic Surgery, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, No. 168, Hongkong Road, Jiang’an District, Wuhan, 430015, Hubei, People’s Republic of China

    Zi Li

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Contributions

LJL conceived and designed this study. WHZ formed the methodology. ZL executed the experiments and analysis of data. LJL and WHZ performed the investigations. ZL drafted the paper. This manuscript was reviewed and revised by LJL and WHZ. This work has been reviewed and approved by all authors.

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Correspondence to Zi Li.

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Consent for publication was acquired from the participants.

Informed Consent

All patients signed the written informed consent.

Research Involving Human and/or Animal Participants

The Clinical Ethics Committee of The Third Hospital of Wuhan (Wuhan, China) granted approval to the present study. The processing of clinical tissue specimens was executed in strict compliance with the ethical standards of the Declaration of Helsinki. All patients signed the written informed consent. The execution of the animal experiment strictly observed the ARRIVE guidelines and was authorized by the Animal Ethics Committee of The Third Hospital of Wuhan.

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Luo, L., Zhang, W. & Li, Z. LncRNA HAGLR May Aggravate Melanoma Malignancy Via miR-4644/ASB11 Pathway. Mol Biotechnol 65, 1619–1631 (2023). https://doi.org/10.1007/s12033-023-00672-8

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