MicroRNA-126 Overexpression Inhibits Proliferation and Invasion in Osteosarcoma Cells

Wang

BioMed Research International

2021

Objective. The aim of the study was to investigate molecular mechanisms underlying the role of miR-126-5p in cisplatin (DDP) sensitivity of non-small-cell lung cancer (NSCLC). Methods. The expression of miR-126-5p and ADAM9 in NSCLC cancer tissues and adjacent tissues, cisplatin-sensitive and drug-resistant NSCLC patient tissues, human normal lung epithelial cells (BESA-2B), human lung adenocarcinoma cell lines A549 and H1560, and cisplatin-resistant mutant cell lines A549/DDP and H1560/DDP was detected by qRT-PCR. After overexpression of miR-126-5p or ADAM9 in A549/DDP and H1560/DDP, MTT and clone formation were used to detect the cell proliferation ability of each treatment group. Flow cytometry was used to detect changes in cell apoptosis. The protein expression of ADAM9 and key molecules of PTEN/PI3K/Akt pathways in cells was measured by western blot. Results. Compared with NSCLC adjacent tissues and NSCLC cisplatin-sensitive tissues, miR-126-5p expression was downregulated in NSCLC tissues and cisplatin-resistant NSCLC tissues and ADAM9 was upregulated. qRT-PCR further detected that miR-126-5p was downregulated in A549, H1560, and their cisplatin-resistant strains A549/DDP and H1560/DDP, while ADAM9 was upregulated. Moreover, overexpression of miR-126-5p inhibited A549/DDP and H1560/DDP cell proliferation and promoted cell apoptosis. The results of dual luciferase showed that miR-126-5p targeted and negatively regulated ADAM9. We also found that overexpression of ADAM9 could reverse the effects of miR-126-5p on NSCLC cell proliferation, apoptosis, and cisplatin sensitivity, and this effect may be achieved by inhibiting the activity of the PTEN/PI3K/Akt signaling pathway. Conclusion. Our data indicated that miR-126-5p may negatively regulate ADAM9 to promote the sensitivity of clinical DDP treatment of NSCLC and be a potential therapeutic target for NSCLC treatment.

Section: Introductionmentioning

confidence: 99%

mir-126-5p Promotes Cisplatin Sensitivity of Non-Small-Cell Lung Cancer by Inhibiting ADAM9

Wang

BioMed Research International

2021

“…Previous studies also reported that miRNAs might target ADAM9 and contribute to diverse biological functions. For example, in osteosarcoma, miR-126 targeted ADAM9 to inhibit cell proliferation and invasion ( 40 ). In hepatocellular carcinoma, ADAM9 might be targeted by miR-1274a ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑30a suppresses the proliferation, migration and invasion of human renal cell carcinoma cells by directly targeting ADAM9

Jiang

2018

Oncol Lett

An increasing number of studies reported that microRNA (miR)-30a was dysregulated in several types of human cancer and may contribute to cancer carcinogenesis and progression. However, its expression and roles in renal cell carcinoma (RCC) remain unknown. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to quantify miR-30a expression in RCC tissues and cell lines. The cell counting kit-8 assay, migration and invasion assays were used to evaluate the roles of miR-30a on the proliferation, migration and invasion of RCC cells. The target gene of miR-30a was identified by luciferase reporter assays, RT-qPCR and western blotting. The results indicated that miR-30a was downregulated in RCC tissues and cell lines compared with corresponding noncancerous tissues and normal renal cell line, respectively. Re-expression of miR-30a inhibited the proliferation, migration and invasion of RCC cells. Additionally, ADAM metallopeptidase domain 9 (ADAM9) was validated as a direct target of miR-30a. Furthermore, the knockdown of ADAM9 by small interfering RNAs was able to mimic the effects of miR-30a overexpression in RCC cells. These results highlight the important role for miR-30a in the occurrence and development of RCC, and the restoration of miR-30a might be investigated as a potential strategy for treating RCC.

“…Our initial results revealed that miR-126 is significantly downregulated, while the mRNA and protein expression of EGFL7 and ERK are upregulated in HCC tissues. MiR-126 expression is downregulated in human cancers, reducing its ability to suppress the proliferative and invasive capacities of cancer cells, such as lung cancer, osteosarcoma, oral cancer and so on [ 11 , 12 , 21 ]. Wong et al have found that miR-126 is significantly decreased in patients carrying hepatitis B and C virus, and lower miR-126 expression predicts poor survival and tumor recurrence for HCC patients after surgery [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of microRNA-126 on cell proliferation, apoptosis and tumor angiogenesis via the down-regulating ERK signaling pathway by targeting EGFL7 in hepatocellular carcinoma

Chen

Fang

et al. 2017

Oncotarget

This study intends to explore the effects of microRNA-126 (miR-126) on cell proliferation, apoptosis, and tumor angiogenesis in hepatocellular carcinoma (HCC) by regulating epidermal growth factor-like domain 7 (EGFL7) through extracellular signal-regulated kinase (ERK) signaling. HCC tissues and adjacent normal tissues were obtained from 184 HCC patients. HCC cells were separately transfected with recombinant plasmids. Western blotting and qRT-PCR were applied to detect miR-126 and EGFL7, ERK, Fas/FasL, Bcl-2, Caspase mRNA and protein levels. CCK8 and TUNEL were performed to determinate cell proliferation and apoptosis. Flow cytometry was used to analyze cell cycle distribution. Rats model of HCC was constructed, and tumor weight and the number of new blood vessels were recorded after 3 weeks of tumor transplantation. Compared with the adjacent normal tissues, HCC tissues exhibited lower miR-126 expression, and higher EGFL7, and ERK mRNA and protein levels. Overexpression of miR-126 in HCC cell lines suppressed EGFL7, ERK, Bcl-2, and P-ERK, and increased apoptotic-associated proteins Fas/FasL and Caspase-3, and it inhibited cell proliferation and induced cell apoptosis. Overexpression of miR-126 in nude mice resulted in reduced tumor weight and less new blood vessels in tumors. The inhibition of miR-126 decreased cell apoptosis, and enhanced cell proliferation and tumor angiogenesis. This study demonstrates that miR-126 might decrease cell proliferation, induce apoptosis, and inhibit tumor angiogenesis in HCC by inhibiting EGFL7 via down-regulating the ERK signaling pathway.