MiR-130a Overcomes Gefitinib Resistance by Targeting Met in Non-Small Cell Lung Cancer Cell Lines

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most common cause of lung cancer death. Currently, the epidermal growth factor receptor inhibitor gefitinib is used for its treatment; however, drug resistance is a major obstacle. Expression of Met has been associated with both primary and acquired resistance to gefitinib, but the mechanisms regulating its expression are not fully understood. Recently, miRNAs such as miR-130a have been shown to play a role in gefitinib resistance, but importance in NSCLC and relationships with Met have not been fully explored. Here we show that miR-130a is over-expressed in gefitinibsensitive NSCLC cell lines, but is low in gefitinib-resistant NSCLC cell lines. Moreover, miR-130a expression was negatively correlated with that of Met. Further analysis revealed that over-expression of miR-130a increased cell apoptosis and inhibited proliferation of NSCLC cells treated with gefitinib, whereas lowering the expression of miR-130a decreased cell apoptosis and promoted cell proliferation after treatment with gefitinib in both gefitinib-sensitive and -resistant NSCLC cell lines, suggesting that miR-130a overcomes gefitinib resistance. We also demonstrated that miR-130a binds to the 3'-UTR of Met and significantly suppresses its expression. Finally, our results showed that over-expressing Met could "rescue" the functions of miR-130a regarding cell apoptosis and proliferation after cells are treated with gefitinib. These findings indicate that the miR-130a/Met axis plays an important role in gefitinib resistance in NSCLC. Thus, the miR-130a/Met axis may be an effective therapeutic target in gefitinib-resistant lung cancer patients.

Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients

“…There were no significant differences between the two groups in terms of gender, age, international prognostic index (IPI) and stage. We investigated the pretreatment concentrations of serum miR-155, miR-200c, miR-29c, miR-130a, miR-145, miR-451, miR-125b and miR-21 expression levels, which have been reported in certain other tumor types to be associated with chemotherapy resistance (Table III) (9,14,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). We observed that only the expression of miR-130a and miR-125b was correlated significantly with the response to chemotherapy.…”

“…A number of previous studies have revealed that miRNAs are involved in the progress of drug resistance in certain types of cancer (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). These miRNAs might play a crucial role in drug resistance by targeting their specific genes.…”

Regulatory Mechanisms of Annexin-Induced Chemotherapy Resistance in Cisplatin Resistant Lung Adenocarcinoma

“…Adenocarcinoma cannot be treated adequately through simple operations. Therefore, chemotherapy remains the mainstay treatments for lung cancer (Wang et al, 2013;Zhou et al, 2014). Cisplatin, as the first line drug, is extensively applied for the clinical treatment of nonsmall-cell lung cancer (Fan and Jiang, 2008).…”

Chicken gga-miR-130a targets HOXA3 and MDFIC and inhibits Marek’s disease lymphoma cell proliferation and migration

“…Studies indicate that miR-130a is associated with lung cancer [50], gastric cancer [51,52], ovarian cancer [53][54][55][56][57], cervical cancer [58,59], and prostate cancer [60]. Recently, deep sequencing technology was used to identify differentially expressed host miRNAs in chickens [28,34,35,61,62].…”