MicroRNA-433 inhibits cervical cancer progression by directly targeting metadherin to regulate the AKT and β-catenin signalling pathways

Abstract

Cervical cancer is one of the most common female malignancies worldwide. Emerging data have shown that microRNAs (miRNAs) play significant roles in various human cancers, including cervical cancer. Aberrantly expressed miRNAs in cervical cancer contribute to tumour occurrence and development as either tumour suppressors or promoters. Research suggests that miRNA-433 (miR-433) possibly plays an important role in the development of various cancer types. However, no study has explored the expression patterns, roles and underlying mechanisms of miR-433 in cervical cancer. In the present study, we demonstrated significant downregulation of miR-433 in cervical cancer tissues and cell lines. Low miR-433 expression was found to significantly correlate with patient characteristics including tumour size, International Federation of Gynecology and Obstetrics stage, lymph node and distant metastases. Functional studies showed that restoration of miR-433 inhibited cell proliferation and invasion and increased apoptosis in cervical cancer cells. Metadherin (MTDH) was also validated as a direct target gene of miR-433. MTDH mRNA expression was upregulated in cervical cancer tissues and was inversely correlated with miR-433 expression. MTDH knockdown showed similar tumour-suppressive roles as miR-433 overexpression in regards to cervical cancer cell proliferation, invasion and apoptosis. Rescue experiments revealed that MTDH overexpression markedly reversed the effects of miR-433 overexpression in regards to proliferation, invasion and apoptosis of cervical cancer cells. Further investigations revealed that miR-433 inactivated AKT and β-catenin pathways in cervical cancer. Collectively, these findings indicate the essential roles of miR-433 in suppressing cervical cancer progression and suggest its potential as a therapeutic target for the treatment of cervical cancer.

Long noncoding RNA ZNF667‐AS1 reduces tumor invasion and metastasis in cervical cancer by counteracting microRNA‐93‐3p‐dependent PEG3 downregulation

“…As a class of small noncoding RNAs, microRNAs (miRNAs) play significant roles in post‐transcriptional gene regulation by targeting the 3′UTR of target messenger RNAs (mRNAs) and decreasing the stability and/or translation of these mRNAs (Bei et al , ). MiRNA dysregulation and its effects have been observed in a variety of human diseases, and various miRNAs can function as potential candidates for CC treatment and prognosis (Liang et al , ; Wang et al , ; Zhou et al , ). In particular, miR‐93 is reported to be involved in CC metastasis and invasion (Wang et al , ).…”

miR‑146a regulates the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis through NF‑κB signaling by targeting TRAF6

“…In addition, it is closely correlated with the susceptibility and clinical prognosis of cervical cancer. miRNAs can regulate the expression of both oncogenes and tumor-suppressor genes (5), thus promoting or inhibiting cancer genesis (6).…”

Lobaplatin inhibits breast cancer progression, cell proliferation while induces cell apoptosis by downregulating MTDH expression

“… 20 , 29 , 33 The evidence on the association of MTDH with microRNAs, AKT, and β-catenin signaling pathways reveals the crucial functional roles of MTDH overexpression in tumorigenesis. 21 , 24 , 25 , 34 , 35 Li et al showed that MTDH was a direct target of tumor suppressor miRNA miR-30a-5p and the overexpression of miR-30a-5p induced hepatocellular carcinoma cell apoptosis via inhibiting MTDH, upregulating PTEN protein, and suppressing Akt. 35 The expression of MTDH was regulated by various tumor suppressing and oncogenic miRNAs.…”

“…MTDH is involved in various pathways 21 , 24 , 25 , 40 . It has been reported that MTDH could promote the differentiation of cancer cell stemness in BCa cells by activating Twist1, thus promoting tumorigenicity.…”