Long Non-Coding RNA HOXA Transcript Antisense RNA Myeloid-Specific 1–HOXA1 Axis Downregulates the Immunosuppressive Activity of Myeloid-Derived Suppressor Cells in Lung Cancer

Abstract

HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is a long non-coding RNA that has been shown to be a key regulator of myeloid cell development by targeting HOXA1. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that possess immunosuppressive function. However, the impact of HOTAIRM1 on the development of MDSCs remains unknown. In this study, we demonstrated that HOTAIRM1 was expressed in MDSCs and that overexpression of HOTAIRM1 could downregulate the expression of suppressive molecules in MDSCs. In addition, HOTAIRM1 levels were observed to be decreased in the peripheral blood cells of lung cancer patients compared with those of healthy controls. By analyzing HOTAIRM1 expression levels in different types of lung cancer, we found that HOTAIRM1 was mainly expressed in lung adenocarcinoma. Finally, it was confirmed that HOTAIRM1 could enhance the expression of HOXA1 in MDSCs and that high levels of HOXA1, the target gene of HOTAIRM1, could delay tumor progression and enhance the antitumor immune response by downregulating the immunosuppression of MDSCs. Taken together, this study illustrates that HOTAIRM1/HOXA1 downregulates the immunosuppressive function of MDSCs and may be a potential therapeutic target in lung cancer.

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

“…HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) is a lncRNA with a length of 1052 bp. It was recently found to participate in various cancers, such as gastrointestinal malignancies [13][14][15][16] , breast cancer 17 , lung cancer 18 , glioblastoma multiforme 19 , and acute myeloid leukemia 20,21 . Of note, HOTAIRM1 is under-expressed in colorectal cancer 13 and gastric cancer 14 .…”

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

“…Additionally, the expression of HOTAIRM1 and its target gene HOXA1 were negatively associated with the ratio of MDSCs and ARG-1 levels in PBMCs of patients with lung cancer. Furthermore, HOTAIRM1 overexpression could decrease the immunosuppressive functions of MDSCs and suppress the induction of MDSCs from PBMCs of healthy control (72). Therefore, HOTAIRM1/HOXA1 might be a potential therapeutic target for lung cancer (72).…”

“…Furthermore, HOTAIRM1 overexpression could decrease the immunosuppressive functions of MDSCs and suppress the induction of MDSCs from PBMCs of healthy control (72). Therefore, HOTAIRM1/HOXA1 might be a potential therapeutic target for lung cancer (72).…”

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

“…Emerging evidences have shown that noncoding RNA (ncRNA) including micro RNA (miRNA), long noncoding RNAs (lncRNAs), and circular RNA are associated with inflammation and tumor, and exert certain regulatory effect on the differentiation and development of MDSCs . In inflammation‐induced tumor, miRNA promote MDSC immunosuppressive functions by activating transcription factor NF‐kB and STAT3 signal, so as to promote angiogenesis, EMT and metastasis, such as miR‐10a, miR‐21, miR‐17‐5p, miR‐20a, miR‐146a, miR‐181b, and so forth .…”