MiR-125a promotes paclitaxel sensitivity in cervical cancer through altering STAT3 expression

Abstract

Cervical cancer (CC) is one of the most common malignancies in women. Paclitaxel is the front-line chemotherapeutic agent for treating CC. However, its therapeutic efficacy is limited because of chemoresistance, the mechanism of which remains poorly understood. Here, we used microRNA (miRNA) arrays to compare miRNA expression levels in the CC cell lines, HeLa and CaSki, with their paclitaxel resistance counterparts, HeLa/PR and CaSki/PR. We demonstrate that miR-125a was one of most significantly downregulated miRNAs in paclitaxel-resistant cells, which also acquired cisplatin resistance. And that the upregulation of miR-125a sensitized HeLa/PR and CaSki/PR cells to paclitaxel both in vitro and in vivo and to cisplatin in vitro. Moreover, we determined that miR-125a increased paclitaxel and cisplatin sensitivity by downregulating STAT3. MiR-125a enhanced paclitaxel and cisplatin sensitivity by promoting chemotherapy-induced apoptosis. Clinically, miR-125a expression was associated with an increased responsiveness to paclitaxel combined with cisplatin and a more favorable outcome. These data indicate that miR-125a may be a useful method to enable treatment of chemoresistant CC and may also provide a biomarker for predicting paclitaxel and cisplatin responsiveness in CC.

The Novel miR-9600 Suppresses Tumor Progression and Promotes Paclitaxel Sensitivity in Non–small-cell Lung Cancer Through Altering STAT3 Expression

“…It has been reported that STAT3 signaling pathway is participated in lung cancer cell proliferation and survival, 47 and STAT3 is also known to involve in cell apoptosis of cervical cancer and glioma. 48,49 Our data also demonstrated that miR-9600 overexpression resulted in decreased expression of STAT3 and then led to cell apoptosis or survival in NSCLC ( Figure 7 ). In the present study, we first focused on cell growth and apoptosis and evaluated the functions of miR-9600 on the downstream genes of the STAT3 signaling pathway.…”

“…48,49,50 Our data also showed that miR-9600 modulates cell motility and metastasis in A549 and SPC-A-1 cells by targeting the STAT3 gene ( Figure 6 ). In addition, miR-9600 expression repressed tumorigenesis in vivo , evidenced by the fact that both mice injected with miR-9600 and si-STAT3 exhibited a decreased tumorigenesis in comparison to the NC- and ASO-9600-injected mice.…”

“…STAT3 is crucial for tumor initiation, development, and progression by regulating gene expression, including the downstream genes of STAT3 signaling pathway during tumorigenesis, 46,47,48,49 STAT3 activation and expression are frequently contributed to the development of tumorigenesis in various types of cancers. 43,47,50 For instance, miR-125a suppresses tumorigenesis in cervical carcinoma through targeting STAT3.…”

Effect of TLR4 on the growth of SiHa human cervical cancer cells via the MyD88‑TRAF6-TAK1 and NF-κB-cyclin D1-STAT3 signaling pathways

“…STAT3 with high degrees of phosphorylation do not exist in normal ovarian epithelial cells lines or benign ovarian tumor cell lines, and abnormal activation of the STAT3 signal transduction pathway may induce a malignant phenotype (23). Previous studies investigating the downstream target gene of the STAT3 transduction pathway have provided increasing evidence, which suggested that the STAT3 transduction pathway serves an important role in a number of processes, including overproliferation, inhibition of apoptosis, vascular reconstruction, invasion and metastasis and drug resistance (24).…”

MicroRNAs in gynecological cancers: Small molecules with big implications

“…A number of other miRNAs, such as miR-106a [278, 279], miR-130b [280], miR-134 [281], miR-145 [282], miR-149 [283], miR-186 [284], miR-197 [285], miR-429 [286], miR-433 [287], miR-490 [288] and miR-591 [278] have been linked to paclitaxel and/or cisplatin resistance in OC. miR-125a [289], miR-224 [290] and miR-375 [291, 292] expression has been linked with paclitaxel resistance in CC cells. Interestingly, although a reduced expression of miR-31 was observed to correlate with paclitaxel resistance [255], its over-expression was reported to drive cisplatin resistance [293].…”