The long noncoding RNA HOXA11‐AS promotes lung adenocarcinoma proliferation and glycolysis via the microRNA‐148b‐3p/PKM2 axis
Abstract Background Lung cancer is the most common malignancy in the world and a growing number of researches have focused on its metabolic characteristics. Studies have shown that the long non‐coding RNA (lncRNA) HOXA11‐AS is aberrantly expressed in many tumors. However, the role of HOXA11‐AS in lu...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-02-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.5103 |
| _version_ | 1797893239595859968 |
|---|---|
| author | Wenkun Chen Xuena Li Bulin Du Yan Cui Yu Ma Yaming Li |
| author_facet | Wenkun Chen Xuena Li Bulin Du Yan Cui Yu Ma Yaming Li |
| author_sort | Wenkun Chen |
| collection | DOAJ |
| description | Abstract Background Lung cancer is the most common malignancy in the world and a growing number of researches have focused on its metabolic characteristics. Studies have shown that the long non‐coding RNA (lncRNA) HOXA11‐AS is aberrantly expressed in many tumors. However, the role of HOXA11‐AS in lung adenocarcinoma (LUAD) glycolysis and other energy metabolism pathways has not been characterized. Method The mRNA levels of HOXA11‐AS, microRNA‐148b‐3p (miR‐148b‐3p), and pyruvate kinase M2 (PKM2) were detected using qRT‐PCR. The expression levels of proteins were measured using immunohistochemistry and western blot. The CCK‐8, EdU, and colony formation assays were used to assess proliferation. Glycolytic changes were assessed by measuring lactate production, ATP production, and 18F‐FDG uptake. Bioinformatics analysis and dual‐luciferase reporter assays were used to characterize the relationship between HOXA11‐AS, miR‐148b‐3p, and PKM2. Proliferation and glycolytic changes were analyzed in xenograft tumor experiments using Micro‐PET imaging after downregulation of HOXA11‐AS in vivo. Results The expression of HOXA11‐AS was markedly increased in LUAD, and was strongly associated with a poor prognosis. In addition, HOXA11‐AS promoted proliferation and glycolysis in LUAD, and miR‐148b‐3p inhibited proliferation and glycolysis in LUAD. Mechanistically, HOXA11‐AS positively regulated PKM2 expression by binding to miR‐148b‐3p, thereby promoting LUAD proliferation and glycolysis. In addition, HOXA11‐AS inhibited LUAD xenograft growth and glycolysis via upregulation of miR‐148b‐3p expression and downregulation of PKM2 expression in vivo. Conclusions These results showed that HOXA11‐AS enhanced LUAD proliferation and glycolysis via the miR‐148b‐3p/PKM2 axis. The findings in this paper expanded our understanding of the molecular mechanisms of LUAD tumorigenesis and glycolysis and showed that HOXA11‐AS could be useful as a diagnostic and prognostic marker for LUAD. 18F‐FDG PET/CT can be used to visually evaluate the therapeutic effect of targeting HOXA11‐AS. |
| first_indexed | 2024-04-10T06:49:42Z |
| format | Article |
| id | doaj.art-a1936bf60796400ea079b8e00fa7bfd5 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-10T06:49:42Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-a1936bf60796400ea079b8e00fa7bfd52023-02-28T08:51:57ZengWileyCancer Medicine2045-76342023-02-011244421443310.1002/cam4.5103The long noncoding RNA HOXA11‐AS promotes lung adenocarcinoma proliferation and glycolysis via the microRNA‐148b‐3p/PKM2 axisWenkun Chen0Xuena Li1Bulin Du2Yan Cui3Yu Ma4Yaming Li5Department of Nuclear Medicine The First Hospital of China Medical University Shenyang ChinaDepartment of Nuclear Medicine The First Hospital of China Medical University Shenyang ChinaDepartment of Nuclear Medicine The First Hospital of China Medical University Shenyang ChinaDepartment of Nuclear Medicine The First Hospital of China Medical University Shenyang ChinaDepartment of Nuclear Medicine The First Hospital of China Medical University Shenyang ChinaDepartment of Nuclear Medicine The First Hospital of China Medical University Shenyang ChinaAbstract Background Lung cancer is the most common malignancy in the world and a growing number of researches have focused on its metabolic characteristics. Studies have shown that the long non‐coding RNA (lncRNA) HOXA11‐AS is aberrantly expressed in many tumors. However, the role of HOXA11‐AS in lung adenocarcinoma (LUAD) glycolysis and other energy metabolism pathways has not been characterized. Method The mRNA levels of HOXA11‐AS, microRNA‐148b‐3p (miR‐148b‐3p), and pyruvate kinase M2 (PKM2) were detected using qRT‐PCR. The expression levels of proteins were measured using immunohistochemistry and western blot. The CCK‐8, EdU, and colony formation assays were used to assess proliferation. Glycolytic changes were assessed by measuring lactate production, ATP production, and 18F‐FDG uptake. Bioinformatics analysis and dual‐luciferase reporter assays were used to characterize the relationship between HOXA11‐AS, miR‐148b‐3p, and PKM2. Proliferation and glycolytic changes were analyzed in xenograft tumor experiments using Micro‐PET imaging after downregulation of HOXA11‐AS in vivo. Results The expression of HOXA11‐AS was markedly increased in LUAD, and was strongly associated with a poor prognosis. In addition, HOXA11‐AS promoted proliferation and glycolysis in LUAD, and miR‐148b‐3p inhibited proliferation and glycolysis in LUAD. Mechanistically, HOXA11‐AS positively regulated PKM2 expression by binding to miR‐148b‐3p, thereby promoting LUAD proliferation and glycolysis. In addition, HOXA11‐AS inhibited LUAD xenograft growth and glycolysis via upregulation of miR‐148b‐3p expression and downregulation of PKM2 expression in vivo. Conclusions These results showed that HOXA11‐AS enhanced LUAD proliferation and glycolysis via the miR‐148b‐3p/PKM2 axis. The findings in this paper expanded our understanding of the molecular mechanisms of LUAD tumorigenesis and glycolysis and showed that HOXA11‐AS could be useful as a diagnostic and prognostic marker for LUAD. 18F‐FDG PET/CT can be used to visually evaluate the therapeutic effect of targeting HOXA11‐AS.https://doi.org/10.1002/cam4.5103aerobic glycolysisHOXA11‐ASlung adenocarcinomamicroRNA‐148b‐3ppyruvate kinase M2 |
| spellingShingle | Wenkun Chen Xuena Li Bulin Du Yan Cui Yu Ma Yaming Li The long noncoding RNA HOXA11‐AS promotes lung adenocarcinoma proliferation and glycolysis via the microRNA‐148b‐3p/PKM2 axis Cancer Medicine aerobic glycolysis HOXA11‐AS lung adenocarcinoma microRNA‐148b‐3p pyruvate kinase M2 |
| title | The long noncoding RNA HOXA11‐AS promotes lung adenocarcinoma proliferation and glycolysis via the microRNA‐148b‐3p/PKM2 axis |
| title_full | The long noncoding RNA HOXA11‐AS promotes lung adenocarcinoma proliferation and glycolysis via the microRNA‐148b‐3p/PKM2 axis |
| title_fullStr | The long noncoding RNA HOXA11‐AS promotes lung adenocarcinoma proliferation and glycolysis via the microRNA‐148b‐3p/PKM2 axis |
| title_full_unstemmed | The long noncoding RNA HOXA11‐AS promotes lung adenocarcinoma proliferation and glycolysis via the microRNA‐148b‐3p/PKM2 axis |
| title_short | The long noncoding RNA HOXA11‐AS promotes lung adenocarcinoma proliferation and glycolysis via the microRNA‐148b‐3p/PKM2 axis |
| title_sort | long noncoding rna hoxa11 as promotes lung adenocarcinoma proliferation and glycolysis via the microrna 148b 3p pkm2 axis |
| topic | aerobic glycolysis HOXA11‐AS lung adenocarcinoma microRNA‐148b‐3p pyruvate kinase M2 |
| url | https://doi.org/10.1002/cam4.5103 |
| work_keys_str_mv | AT wenkunchen thelongnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT xuenali thelongnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT bulindu thelongnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT yancui thelongnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT yuma thelongnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT yamingli thelongnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT wenkunchen longnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT xuenali longnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT bulindu longnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT yancui longnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT yuma longnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis AT yamingli longnoncodingrnahoxa11aspromoteslungadenocarcinomaproliferationandglycolysisviathemicrorna148b3ppkm2axis |