MicroRNA-130a targeting hypoxia-inducible factor 1 alpha suppresses cell metastasis and Warburg effect of NSCLC cells under hypoxia.

MicroRNAs have been demonstrated to play critical role in the development of non-small cell lung cancer (NSCLC) and hypoxia is a common hallmark of NSCLC. MiRNA-130a-3p (miR-130a) is a well-known tumor suppressor, and we intended to explore the role and mechanism of miR-130a in NSCLC cells under hypoxia. We used real-time quantitative polymerase chain reaction method to measure miR-130a expression, and found that miR-130a was downregulated in human NSCLC tumors and cell lines (A549 and H1299), accompanied with upregulation of hypoxia-inducible factor 1 alpha (HIF1A), a marker of hypoxia. Besides, miR-130a low expression was associated with tumor burden and poor overall survival. Moreover, miR-130a expression was even downregulated in hypoxia-treated A549 and H1299 cells. Ectopic expression of miR-130a suppressed Warburg effect, migration and invasion in hypoxic A549 and H1299 cells, as evidenced by decreased glucose consumption, lactate production, hexokinase 2 expression, and numbers of migration cells and invasion cells analyzed by commercial glucose and lactate assay kits, western blotting and transwell assays. Furthermore, overexpression of miR-130a restrained xenograft tumor growth of A549 cells in mice. However, recovery of HIF1A could reverse the suppressive effect of miR-130a overexpression on cell migration, invasion and Warburg effect in hypoxic A549 and H1299 cells. Mechanically, dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assay confirmed a target relationship between miR-130a and HIF1A. Collectively, we demonstrated an anti-tumor role of miR-130a in NSCLC cells under hypoxia through targeting HIF1A, suggesting a potential target for the interfering of NSCLC.

Shi J ，Wang H ，Feng W ，Huang S ，An J ，Qiu Y ，Wu K ... -  《-》

LncRNA HOTAIR knockdown inhibits glycolysis by regulating miR-130a-3p/HIF1A in hepatocellular carcinoma under hypoxia.

High rate of glycolysis supports hepatocellular carcinoma (HCC) cell growth even in a hypoxic environment. However, the mechanism underlying glycolysis under hypoxia remains largely unknown. Long noncoding RNAs (lncRNAs) play essential roles in regulating glucose metabolism in cancers. This study aimed to explore the role of lncRNA homeobox transcript antisense RNA (HOTAIR) in HCC glycolysis under hypoxia. Thirty-eight HCC patients were recruited. HepG2 and Huh7 cells were used for study in vitro. The expression levels of HOTAIR, microRNA-130a-3p (miR-130a-3p) and hypoxia inducible factor 1 alpha (HIF1A) were measured by quantitative real-time polymerase chain reaction and western blot, respectively. The glycolysis under hypoxia (1 % O2) condition was investigated by glucose consumption, lactate production and hexokinase 2 (HK2) level. The target interaction between miR-130a-3p and HOTIR or HIF1A was analyzed by bioinformatics analysis, luciferase assay, RNA pull-down and RNA immunoprecipitation. We found that HOTAIR expression was enhanced in HCC tissues and cells. Under hypoxia condition, HOTAIR expression was increased and its knockdown inhibited glycolysis in HCC cells. HOTAIR was validated as a decoy of miR-130a-3p and miR-130a-3p deficiency reversed the suppressive effect of HOTAIR silence on glycolysis under hypoxia. HIF1A was indicated as a target of miR-130a-3p and miR-130a-3p overexpression repressed glycolysis under hypoxia by targeting HIF1A. Moreover, HIF1A expression was regulated by HOTAIR and miR-130a-3p. In conclusion, knockdown of HOTAIR suppressed glycolysis by regulating miR-130a-3p and HIF1A in HCC cells treated by hypoxia, elucidating a novel mechanism in HCC glycolysis.

Hu M ，Fu Q ，Jing C ，Zhang X ，Qin T ，Pan Y ... -  《-》

A Regulatory Axis of circ_0008193/miR-1180-3p/TRIM62 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Lung Adenocarcinoma Cells Under Hypoxia.

Chen M ，Huang X ，Li L ，Huang M ，Cai R ，Liao X ... -  《MEDICAL SCIENCE MONITOR》

MiR-206 may suppress non-small lung cancer metastasis by targeting CORO1C.

Non-small lung cancer (NSCLC), with a poor 5-year survival rate (16%), is the major type of lung cancer. Metastasis has been identified as the main factor that leads to NSCLC therapy failure. MiR-206 is a metastasis suppressor in many cancers, including colorectal cancer, renal cell carcinoma and breast cancer. However, the role of miR-206 in NSCLC metastasis and the underlying mechanism are still obscure. Quantitative reverse-transcription PCR (q-RT-PCR) assay was used to detect miR-206 mRNA of NSCLC tissues and lung cancer lines. The MTT assay, scratch wound healing assay, transwell migration assay and transwell invasion assay were conducted to illuminate the effect of miR-206 on A549 cells' proliferation, migration and invasion. Gaussia luciferase reporter assay, q-RT-PCR and western blotting assay were used to explore the underlying mechanism. Also, the A549 xenograft model was conducted to evaluate the anti-tumor effect of miR-206 in vivo. The results showed that miR-206 expression was decreased in NSCLC tissues and lung cancer cells. Further research demonstrated that miR-206 inhibited the proliferation, migration and invasion of A549 cells via negatively regulating Coronin-1C (CORO1C), and CORO1C deletion significantly rescues the miR-206 mediated inhibitory effect on A549 cells. Moreover, miR-206 exhibited a perfect anti-tumor effect in the A549 xenograft model. Our study reveals that miR-206 functions as a tumor metastasis suppressor and sheds new light on the clinical significance of miR-206 in NSCLC therapy.

Liao M ，Peng L 《-》

MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway.

Wei CH ，Wu G ，Cai Q ，Gao XC ，Tong F ，Zhou R ，Zhang RG ，Dong JH ，Hu Y ，Dong XR ... -  《Journal of Hematology & Oncology》