MicroRNA‐378‐3p/5p represses proliferation and induces apoptosis of oral squamous carcinoma cells via targeting KLK4

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck neoplasm. Down‐regulation of hsa‐microRNA‐378 (miR‐378) has been proved in OSCC tissues, suggesting that miR‐378 might play crucial roles in the progression of OSCC. The present study aimed to evaluate the effect of miR‐378‐3p/5p on the proliferation and apoptosis of OSCC in vitro and in vivo. According to the results, lentivirus‐mediated overexpression of miR‐378 lowered the colony formation efficiency, blocked cell cycle progression, and decreased the percentage of Ki‐67 positive cells, whereas knockdown of miR‐378‐3p/5p led to the opposite results. Furthermore, the apoptosis of OSCC cells was induced by the overexpression of miR‐378 as evidenced by decreasing Bcl‐2/Bax ratio, increasing cleaved caspase‐9, cleaved caspase‐3, and cleaved PARP levels, and promoting the release of cytochrome c into the cytoplasm. However, the above results were reversed by miR‐378‐3p/5p silencing. In addition, the overexpression of miR‐378 inhibited the activation of PI3K/AKT signalling pathway. Conversely, miR‐378‐3p/5p knockdown resulted in the inactivation of PI3K/AKT signalling pathway. Mechanically, we validated that miR‐378‐3p/5p could target kallikrein‐related peptidase 4 (KLK4), and enforced overexpression of KLK4 counteracted miR‐378 overexpression‐induced apoptosis. Finally, tumourigenesis in nude mice was suppressed by the overexpression of miR‐378, which was promoted by miR‐378‐3p/5p silencing. Taken together, these results suggest that miR‐378 may be a potential target in the diagnoses and treatment of OSCC.

NCAPG, mediated by miR-378a-3p, regulates cell proliferation, cell cycle progression, and apoptosis of oral squamous cell carcinoma through the GSK-3β/β-catenin signaling

“…These findings indicated that -catenin signaling pathway by promoting -catenin, thereby affecting OSCC progression. Intriguingly, our lab previously reported that miR-378-3p/5p represses the proliferation and metastasis of oral squamous carcinoma cells by inhibiting KLK4 [29,30]. By using online prediction software, we found that NCAPG may also be a target gene of miR-378a-3p (previously miR-378).…”

Non-Coding RNAs and Oral Cancer: Small Molecules With Big Functions

“…Conversely, inhibition of miR-378-3p/5p expression obtained the opposite results. These results suggested that miR-378 participated in the dysregulation of proliferation and apoptosis in OSCC cells ( 119 ).…”

“…In addition, miR-378 overexpression was resulted in a decreased p-AKT level, whereas miR-378-3p/5p silencing could raise the p-AKT level in OSCC cells. Therefore, the PI3K/AKT signaling pathway was involved in the regulatory mechanisms of miR378 in OSCC ( 119 ). In addition, as shown in Figure 1 , miR-29b suppresses proliferation, migration, and induces apoptosis of tongue squamous cell carcinoma through PTEN–AKT signaling pathway by targeting Sp1.…”

“…Subsequently, PARP, as a substrate of caspase-3, is cleaved and activated to induce apoptosis (118). Recently, Cui et al (119) investigated the regulation of miR-378 in the mitochondrial-mediated apoptotic signaling pathway of oral squamous carcinoma cells (OSCC). The results of their study showed that overexpression of miR-378 suppressed the proliferation and induced apoptosis of OSCC cells, while knockdown of miR-378-3p/5p led to the opposite results.…”

Roles of Mitochondria in Oral Squamous Cell Carcinoma Therapy: Friend or Foe?

“…For example, delivering microRNA-125 with ellagic acid to mitochondria could promote TSCC cell death by reducing antiapoptotic protein expression and increasing proapoptotic protein expression [ 141 ]. In addition, the overexpression of microRNA-378 could decrease the Bcl-2/Bax ratio by inactivating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, which induces the MAP of OSCC [ 142 ].…”