miR‑139‑5p enhances cisplatin sensitivity in non‑small cell lung cancer cells by inhibiting cell proliferation and promoting apoptosis via the targeting of Homeobox protein Hox‑B2

Abstract

The development of chemotherapeutic dug resistance hinders the clinical treatment of cancer. Micrornas (mirnas/mirs) have been revealed to serve essential roles in the drug resistance of numerous types of cancer. mir-139-5p was previously reported to be associated with cisplatin (ddP) sensitivity in human nasopharyngeal carcinoma cells and colorectal cancer cells. However, the effect and underlying mechanism of mir-139-5p in ddP sensitivity in non-small cell lung cancer (nSclc) cells has not yet been fully elucidated. in the present study, the expression of mir-139-5p and Homeobox protein Hox-B2 (HoXB2) in nSclc tissues was examined by reverse transcription-quantitative polymerase chain reaction (rT-qPcr) and western blotting. Subsequently, the effect of mir-139-5p on the ddP sensitivity of nSclc cells in vitro was investigated. cell proliferation was examined using a cell counting Kit-8 assay. Western blotting was used to evaluate the protein expression of HoXB2, phosphorylated (p)-Pi3K, p-aKT, caspase-3 and cleaved-caspase-3, and rT-qPcr was used to evaluate the expression of mir-139-5p, and the mrna expression levels of HoXB2, Pi3K, aKT and caspase-3. The apoptotic rate of the cells was detected using flow cytometry. miR-139-5p expression in NSCLC tissues was shown to be significantly lower compared with that in adjacent tissues. additionally, mir-139-5p increased cell apoptosis and inhibited nSclc cell proliferation induced by ddP in vitro via modulating the Pi3K/aKT/caspase-3 signaling pathway. Furthermore, HOXB2 was identified to be a target of mir-139-5p, and mir-139-5p was revealed to sensitize nSclc cells to ddP via the targeting of HoXB2. Taken together, the results of the present study demonstrated that regulating the expression of mir-139-5p could provide a novel approach to reverse ddP resistance and increase chemosensitivity in the treatment of nSclc.

RETRACTED ARTICLE: Circular RNA SOX13 promotes malignant behavior and cisplatin resistance in non-small cell lung cancer through targeting microRNA-3194-3p/microtubule-associated protein RP/EB family member 1

“…NSCLC is allocated into three different subtypes, including squamous cell carcinoma, adenocarcinoma and large cell lung carcinoma [ 4 ]. Treating NSCLC mainly relies on surgical resection and chemotherapy or radiation therapy [ 5 , 6 ]. However, due to the acquired resistance, the clinical effect and prognosis of NSCLC are still poor [ 7 , 8 ].…”

Integrated Tissue and Blood miRNA Expression Profiles Identify Novel Biomarkers for Accurate Non-Invasive Diagnosis of Breast Cancer: Preliminary Results and Future Clinical Implications

“…Tang et al found that hsa-miR-139-5p increased apoptosis and inhibited cisplatin (DDP), induced non-small cell lung cancer (NSCLC) cell proliferation in vitro by regulating the PI3K/AKT/caspase-3 signaling pathway, and sensitized NSCLC cells to DDP by targeting HOXB2 . Modulation of hsa-miR-139-5p expression reversed DDP resistance and increased chemosensitivity of therapeutic NSCLC [ 82 ]. Furthermore, Fentanyl can inhibit the viability and invasion of NSCLC cells by inducing hsa-miR-331-3p and reducing HDAC5 [ 83 ].…”

Transcription factor HOXB2 upregulates NUSAP1 to promote the proliferation, invasion and migration of nephroblastoma cells via the PI3K/Akt signaling pathway

“…a previous study demonstrated that HoXB2 served an important role in the proliferation, invasion and migration of ovarian cancer cells (9). in addition, microrna-139-5p attenuated the proliferation of lung cancer cells via targeting HoXB2 (10). Furthermore, another study revealed that HoXB2 could promote the apoptosis of gastric cancer cells and enhance their sensitivity to cisplatin (10).…”

“…in addition, microrna-139-5p attenuated the proliferation of lung cancer cells via targeting HoXB2 (10). Furthermore, another study revealed that HoXB2 could promote the apoptosis of gastric cancer cells and enhance their sensitivity to cisplatin (10). Jing et al (11) demonstrated that HoXB2 and forkhead box c1 (FoXc1) were upregulated in nephroblastoma tissues, while their expression was closely associated with tumor stage and lymph node metastasis.…”