Related Experiment Video

Updated: Jan 11, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

The LBX2-AS1-miR-491-5p-PKM2 Positive Feedback Loop Promotes Radiation Resistance of Esophageal Cancer by Enhancing

Fuhui Zhang¹, Zhiwu Wang², Xuemin Yao^3,4

¹Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China, tjmugh.com.cn.

Biomed Research International

|November 17, 2025

Abstract

Background And Objective:

Radioresistance is a significant factor affecting the therapeutic efficacy of radiotherapy. This study is aimed at investigating the molecular mechanism by which LBX2-AS1 regulates pyruvate kinase M2 (PKM2) to influence radioresistance and its potential as a biomarker for radioresistance in esophageal cancer.

Methods And Key Findings:

Radioresistant sub-cell lines, KYSE150R, were established in KYSE150 cells, and PKM2, cyclin D1, HIF-1α, and LBX2-AS1 levels were elevated in KYSE150R. Upregulated and downregulated PKM2 sub-cell lines were established. Upregulating PKM2 increased the PKM2 level in the nucleus and increased levels of HIF-1α, cyclin D1, and LBX2-AS1. The knockdown of PKM2 showed the opposite result. Downregulated LBX2-AS1 sub-cell lines were established. Downregulation of LBX2-AS1 decreased cell proliferation, glycolysis, cell cycle progression, and radioresistance, along with a reduction in cyclin D1, HIF-1α, and PKM2 levels. The dual-luciferase reporter system was used to verify that LBX2-AS1 directly binds to miR-491-5p, and miR-491-5p directly binds to the 3 ^'UTR of PKM2 mRNA. Downregulation of miR-491-5p in sh-LBX2-AS1 cells could increase cell proliferation, cell cycle, glycolysis, and radiation resistance. The LBX2-AS1 level in serum of patients with esophageal cancer was detected, and its clinical relevance was analyzed. Results showed that high LBX2-AS1 levels correlated with worse disease control, increased lymphatic metastasis, and poorer overall and progression-free survival.

Conclusion And Clinical Implications:

LBX2-AS1-miR-491-5p-PKM2 positive feedback loop enhances the radioresistance of esophageal cancer cells by altering the cell cycle and enhancing glycolysis. High level of LBX2-AS1 in serum was correlated with worse DCR, lymphatic metastasis, worse overall survival, and progression-free survival.

Keywords:

LBX2-AS1 PKM2 esophageal cancer glycolysis radiotherapy

More Related Videos

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line

Published on: April 11, 2025

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids

Published on: December 23, 2022

Related Concept Videos

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

mTOR Signaling and Cancer Progression

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

Mitogens and the Cell Cycle

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...

Articles linked to this work by shared authors, journal, and citation graph.

Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma.

PLoS genetics·2019

See all related articles