Overexpression of microRNA-133b sensitizes non-small cell lung cancer cells to irradiation through the inhibition of glycolysis

Abstract

Abstract. Non-small cell lung cancer (NSCLC) accounts for 85% of all types of lung cancer and is the leading cause of world-wide cancer-associated mortalities. Radiation therapy has long been regarded as a fundamental therapeutic treatment strategy for NSCLC. However, alternative therapies for NSCLC remain insufficient, with the majority of cancers developing a high incidence of radioresistance. MicroRNAs (miRNAs/miRs) are endogenous oligonucleotide RNAs that serve an important role in carcinogenesis and tumor progression. In the present study, a novel function of miR-133b that is associated with the radiosensitivity of lung cancer cells is reported. miR-133 was downregulated in radioresistant lung cancer cells, which exhibited an elevated glycolysis rate when compared with radiosensitive cells. Additionally, it was observed that pyruvate kinase isoform M2 (PKM2) is a target of miR-133b, and that the expression of PKM2 is positively correlated with radioresistance. Finally, it was demonstrated that overexpression of miR-133b resensitizes radioresistant lung cancer cells through the inhibition of PKM2-mediated glycolysis. The current study may indicate a novel function of miR-133b, potentially aiding the development of anticancer therapeutics.

miR‐155‐5p and miR‐760 mediate radiation therapy suppressed malignancy of non‐small cell lung cancer cells

“…Previous studies revealed that a growing number of miRNAs are involved in the radiosensitivity of cancers including NSCLC . In lung cancer cells, overexpression of miR‐133b can sensitize radioresistant lung cancer cells by inhibiting pyruvate kinase isoform M2 (PKM2)‐mediated glycolysis . Downregulation of miR‐21 can reverse the radiosensitivity of NSCLC cells via targeting tumor suppressor PTEN .…”

Knockdown of Lncrna PVT1 Enhances Radiosensitivity in Non-Small Cell Lung Cancer by Sponging Mir-195

“…For example, Liu et al found that miR-133b overexpression sensitized radioresistant lung cancer cells by inhibiting pyruvate kinase isoform M2 (PKM2)-mediated glycolysis [28]. Liu et al reported that miR-21 downregulation inhibited cell growth, metastasis and reversed chemo- and radio-sensitivity of NSCLC cells by targeting tumor suppressor PTEN [29].…”

miR-206/133b Cluster: A Weapon against Lung Cancer?

“… 33 miR-133b was also verified to correlate with radiation therapy in lung cancer cells, and it was low expressed in radioresistant lung cancer cells. 72 Elevating expression of miR-133b contributed to radioresistant lung cancer cells being resensitive, and the relevant pathway was involved in pyruvate kinase isoform M2-mediated glycolysis. 72 In addition, Wu et al.…”

“… 72 Elevating expression of miR-133b contributed to radioresistant lung cancer cells being resensitive, and the relevant pathway was involved in pyruvate kinase isoform M2-mediated glycolysis. 72 In addition, Wu et al. 73 demonstrated that cationic lipids combined with pre-miR-133b significantly elevated the level of mature miR-133b in the lung cancer A549 cell and in the mouse model.…”