Down-Regulation of miR-7 in Gastric Cancer Is Associated With Elevated LDH-A Expression and Chemoresistance to Cisplatin

Abstract

MicroRNAs (miRNAs) are dysregulated in the context of many cancer types, making them potentially ideal diagnostic or therapeutic targets in patients in which they are aberrantly expressed. In the present study, we found miR-7 to be downregulated in gastric cancer (GC), and we further determined its expression to be closely linked to GC sensitivity to the chemotherapeutic compound cisplatin. This effect appears to be at least partially attributable to the regulation of LDH-A, which is a miR-7 target gene and expression of LDH-A is negatively correlated with miR-7 expression in primary GC tumor samples. When upregulated, we also determined that miR-7 was able to inhibit the proliferation, colony formation, and glycolysis of GC cells owing to its regulation of LDH-A. Moreover, overexpression of miR-7 render cells more sensitive to cisplatin. Our results thus provide novel evidence that miR-7 is a key mediator of GC growth and chemosensitivity through its regulation of LDH-A, thus potentially highlighting this pathway as a therapeutic target for treating affected patients.

High Pretreatment LDH Predicts Poor Prognosis in Hypopharyngeal Cancer

“…The inhibition of LDH resulted in reduced cell proliferation ( 19 ). Former research studies showed that LDH not merely associates with the activation of some proto-oncogenes, such as Myc and HIF- α ( 20 ), but also plays a crucial role in the maintenance of tumor invasiveness ( 21 , 22 ), metastatic potential ( 23 , 24 ), chemoresistance ( 25 ), and radioresistance ( 26 ). Moreover, it also showed that LDH takes part in immunosuppression ( 27 ), and LDH can be regarded as an immune surveillance prognostic marker ( 28 ) and its abnormal rise was forerunner of unfavorable outcomes in cancer patients ( 29 ).…”

Prognostic Factor in Patients with Advanced, Inoperable Thymic Carcinoma: An Application of the Lung Immune Prognostic Index

“…LDH plays an unfavorable role in various cancers; it is reportedly associated with tumor invasion and proliferation [19] , metastatic potential [20] , and drug resistance [21] . Elevated dNLR indicates a preference for granulocytes and monocytes over lymphocytes, re ecting the promotion of in ammatory dynamics in the tumor microenvironment [6] .…”

MiR-7 in Cancer Development

“…Similar pathways were influenced in tongue squamous cell carcinoma [ 71 ]. Recently it was found that miR-7 could target lactate dehydrogenase A (LDH-A) in gastric cancer cells, so its downregulation can influence glycolysis, cell proliferation and sensitivity to chemotherapy [ 150 ].…”