c-Myc suppresses microRNA-29b to promote tumor aggressiveness and poor outcomes in non-small cell lung cancer by targeting FHIT

Abstract

The dual role of the microRNA-29 (miR-29) family in tumor progression and metastasis in solid tumors has been reported. Evidence for the role of miR-29 in tumor malignancy and its prognostic value in overall survival (OS) and relapse-free survival (RFS) in non-small cell lung cancer (NSCLC) remains conflicting. Mechanistic studies presented herein demonstrated that c-Myc suppressed the expression of miR-29b, promoting soft agar growth and invasion capability in lung cancer cells. Interestingly, the decrease in the expression of miR-29b by c-Myc is responsible for soft agar growth and invasiveness mediated by FHIT loss due to promoter methylation. Among patients, low expression of miR-29b and FHIT was more common in tumors with high c-Myc expression than in tumors with low c-Myc expression. Kaplan-Meier and Cox regression analysis showed that tumors with high c-Myc, low miR-29b and low FHIT expression had shorter OS and RFS periods than their counterparts. In conclusion, the decrease in the expression of miR-29b by c-Myc may be responsible for FHIT loss-mediated tumor aggressiveness and for poor outcome in NSCLC. Therefore, we suggest that restoration of the miR-29b expression using the c-Myc inhibitor might be helpful in suppressing tumor aggressiveness mediated by FHIT loss and consequently improving outcomes in NSCLC patients with tumors with low expression of FHIT.

RETRACTED ARTICLE: Cell-specific delivery of messenger RNA and microRNA by recombinant MS2 virus-like particles carrying cell-penetrating peptide

“…MiR-29b is known to induce tumor cell apoptosis (Huang et al 2013;Poudyal et al 2013;Wu et al 2014); therefore, we investigated whether the miR-29b packaged in MS2 VLPs could induce apoptosis in HeLa, A549, and Kasumi-1 cells. As shown in Fig.…”

Effect of microRNA-135a on Cell Proliferation, Migration, Invasion, Apoptosis and Tumor Angiogenesis Through the IGF-1/PI3K/Akt Signaling Pathway in Non-Small Cell Lung Cancer

“…Additionally, miR-135a exhibits its tumor suppressive function by negatively regulating c-Myc, JAK2 and ROCK1 [16-18]. c-Myc is an oncogene that can enhance the aggressiveness of tumors and is responsible for poor outcomes in NSCLC patients [31]. A significant positive correlation has been found between JAK2 activation and lung cancer grade.…”

MicroRNA-29c Functions as a Tumor Suppressor by Targeting VEGFA in Lung Adenocarcinoma

“…MiR-29 family has been observed to be aberrently expressed in different types of cancer and be involved in biological functions including cell proliferation, cell cycle, senescence, differentiation, apoptosis and metastasis [19]. As for lung cancer, growing evidence indicates that miR-29 family functions as tumor suppressor and most studies focus on the biology of miR29b [8,[20][21][22][23]. However, despite the high similarity of miR-29a/b/c mature sequence, studies have revealed that different isoforms of miR-29 family may exert distinct functions [24,25].…”