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MicroRNA?126?3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway.

ABSTRACT: We previously reported that relative to normal cervical mucus, microRNA 126?3p (miR?126?3p) is present in significantly greater amounts in the cervical mucus of patients with overt cervical cancer or precursor lesions. Here, we investigated the effects of enforced miR?126?3p expression in the cervical cancer cell line, HeLa, on proliferation, migration, invasion, apoptosis and protein expression. We transfected HeLa cells with miR?126?3p miRNA and found that proliferation, migration and invasion by cell counting, wound healing, cell migration and invasion assay were significantly reduced in these cells relative to those transfected with a negative control mimic. The levels of phosphoinositide 3 kinase (PI3K), phosphorylated 3?phosphoinositide?dependent protein kinase?1 (p?PDK1) and p?AKT proteins were lower in the miR?126?3p?transfected cells. Phosphorylated 70S6K (p?p70S6K), phosphorylated glycogen synthase kinase 3? (p?GSK3?), phosphorylated S6K (p?S6K), cyclin D1, phosphorylated p21?activated kinase 1 (p?PAK1), Rho associated coiled?coil containing protein kinase 1 (ROCK1), myotonic dystrophy?related CDC42?binding kinases ? (MRCK?) and phospholipase C ?1 (p?PLC?1) were also downregulated. This suggests that downstream effectors of the PI3K/PDK1/AKT pathway are targets for inhibition by miR?126?3p. In contrast, apoptotic?related proteins including the BCL?2?associated agonist of cell death (Bad), B?cell lymphoma?extra?large (Bcl?xL) and BCL?2?associated X (Bax), were all upregulated by miR?126?3p, resulting in increased caspase 3/7 activity and apoptosis. Thus, enforced expression of miR?126?3p inhibited cell migration and invasion and also induced apoptosis by regulating the PI3K/PDK1/AKT pathway in HeLa cells. Hence, high levels of miR?126?3p may inhibit cervical carcinogenesis, and targeting the PI3K/PDK1/AKT pathway via miR?126?3p could represent a new approach for treating patients with cervical cancer.

SUBMITTER: Ichikawa R

PROVIDER: S-EPMC7057934 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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MicroRNA‑126‑3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway.

Ichikawa Ryoko R Kawasaki Rie R Iwata Aya A Otani Sayaka S Nishio Eiji E Nomura Hiroyuki H Fujii Takuma T

Oncology reports 20200221 4

We previously reported that relative to normal cervical mucus, microRNA 126‑3p (miR‑126‑3p) is present in significantly greater amounts in the cervical mucus of patients with overt cervical cancer or precursor lesions. Here, we investigated the effects of enforced miR‑126‑3p expression in the cervical cancer cell line, HeLa, on proliferation, migration, invasion, apoptosis and protein expression. We transfected HeLa cells with miR‑126‑3p miRNA and found that proliferation, migration and invasion ...[more]

PMID: 32323808

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Project description:BackgroundUFM1 has been found to be involved in the regulation of tumor development. This study aims to clarify the role and potential molecular mechanisms of UFM1 in the invasion and metastasis of gastric cancer.MethodsExpression of UFM1 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was analyzed by Western blotting, immunohistochemistry, and realtime PCR. Its correlation with the clinicopathological characteristics and prognosis of gastric cancer patients was analyzed. The effects of UFM1 on the invasion and migration of gastric cancer cells were determined by the wound and trans-well assays, and the effect of UFM1 on subcutaneous tumor formation was verified in nude mice. The potential downstream targets of UFM1 and related molecular mechanisms were clarified by the human protein kinase assay and co-immunoprecipitation technique.ResultsCompared with the corresponding adjacent tissues, the transcription level and protein expression level of UFM1 in gastric cancer tissues were significantly downregulated (P?<?0.05). The 5-year survival rate of gastric cancer patients with low UFM1 expression was significantly lower than the patients with high UFM1 expression (42.1% vs 63.0%, P?<?0.05). The invasion and migration abilities of gastric cancer cells with stable UFM1 overexpression were significantly decreased, and the gastric cancer cells with UFM1 stable knockdown showed the opposite results; similar results were also obtained in the nude mouse model. Further studies have revealed that UFM1 could increase the ubiquitination level of PDK1 and decrease the expression of PDK1 at protein level, thereby inhibiting the phosphorylation level of AKT at Ser473. Additionally, the effect of UFM1 on gastric cancer cell function is dependent on the expression of PDK1. The expression level of UFM1 can improve the poor prognosis of PDK1 in patients with gastric cancer.ConclusionUFM1 suppresses the invasion and metastasis of gastric cancer by increasing the ubiquitination of PDK1 through negatively regulating PI3K/AKT signaling.

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MicroRNA?126?3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway.

Publications

MicroRNA‑126‑3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway.

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