miR-424-5p regulates cell proliferation and migration of esophageal squamous cell carcinoma by targeting SIRT4

Abstract

Objective: The present research is aimed to elucidate the expression patterns of miR-424-5p and its role in tumorigenesis and progression of esophageal squamous cell carcinoma (ESCC). Methods: Both starBase and TCGA were utilized to assess miR-424-5p expression status in ESCC. The endogenous mRNA expression levels of miR-424-5p in ESCC and normal esophagus cell lines were detected by qRT-PCR. CCK8 and colony-forming assays were applied to determine the effects of miR-424-5p on ESCC proliferation. Transwell migration and wound healing assays were carried out to observe the changes of ESCC cell mobility after miR-424-5p mimic or inhibitor transfection. Impact of miR-424-5p on malignancy growth in vivo was further verified in a mouse xenograft model. The regulatory relationships between miR-424-5p and SIRT4 were validated by dual luciferase reporter assay, qRT-PCR and Western blot. Results: miR-424-5p expression was found upregulated in ESCC. miR-424-5p overexpression dramatically facilitated ESCC cells proliferation and migration capacity in vitro, while downregulation of miR-424-5p displayed the opposite trend. Inhibition of xenograft tumor growth was further evidenced in vivo. Moreover, SIRT4 was confirmed to be a specific target gene of miR-424-5p in ESCC and negatively modulated by miR-424-5p. Finally, SIRT4 overexpression strongly rescued the promoting influence of miR-424-5p on the proliferative and migratory capacity of ESCC cells. Conclusions: miR-424-5p had tumor promoting functions in proliferation and migration of ESCC by targeting SIRT4, suggesting that miR-424-5p may serve as a potential diagnostic biomarker and manipulation of miR-424-5p/SIRT4 axis could provide a novel therapeutic strategy for further ESCC treatment.

The role of long non-coding RNAs in angiogenesis and anti-angiogenic therapy resistance in cancer

“…MiR-424-5p has the dual effects of oncogene and tumor suppressor gene. In LSCC, 86 esophageal cancer, 87 CRC, 88 and thyroid cancer, 89 miR-424-5p mainly intensifies the proliferation, invasion, migration, and drug resistance of tumor cells. However, it has the opposite effect on liver, 90 breast, 91 and nasopharyngeal cancers.…”

Role of sirtuins in esophageal cancer: Current status and future prospects

“…In EC, SIRT4 has been reported as a tumor suppressor (Table 2 ). Cui et al [ 76 ] revealed that SRT4 was negatively regulated by miR-424-5p, and overexpression of SIRT4 strongly rescued the promoting effect of miR-424-5p on ESCC cell proliferation and migration capacity. In addition, Nakahara et al [ 77 ] reported that a low SIRT4 expression was significantly associated with a high distant recurrence rate and poor prognosis, and in vitro , knockdown of SIRT4 promoted glutamine dehydrogenase activity and stimulated cell proliferation and migration.…”

Sequence Requirements for miR-424-5p Regulating and Function in Cancers

“…Ying [ 91 ] found that the expression of miR-424-5p is upregulated in ESCC tissues and that the overexpression of miR-424-5p can promote the proliferation and migration of ESCC through the targeted regulation of SIRT4. SIRT4 is a member of the SIRT family [ 37 ] and has been proven to play an important role in longevity and metabolism.…”