PLAG1 silencing promotes cell chemosensitivity in ovarian cancer via the IGF2 signaling pathway

Abstract

Ovarian cancer (Oc) is one of the most lethal gynecological diseases. Novel prognostic biomarkers and therapeutic targets for Oc are urgently required. The aim of this study was to investigate the mechanisms that govern how pleomorphic adenoma gene 1 (PLAG1) influences the biological processes and chemosensitivity of Oc cells via the insulin-like growth factor-2 (IGF2) signaling pathway. differentially expressed genes in Oc were selected based on bioinformatics data. Oc and adjacent tissue specimen were collected, followed by the determination of the expression of PLAG1 and IGF2 signaling pathway-associated genes. The regulatory mechanisms of PLAG1 in Oc cells were analyzed following treatment with pcdNA or small interfering RNA (siRNA), and included the assessment of cell proliferation, migration, invasion and cisplatin resistance. PLAG1 was identified as an upregulated gene in OC. OC tissues exhibited increased expression of PLAG1 and IGF2 compared with the controls. Moreover, PLAG1 was observed to positively regulate the IGF2 signaling pathway. The siRNA-mediated silencing of PLAG1 resulted in decreased expression of IGF2, IGF1 receptor and insulin receptor substrate 1, as well as inhibited proliferation, migration, invasion and cisplatin resistance of Oc cells. Furthermore, the effect of PLAG1 was dependent on IGF2. PLAG1 may therefore be considered as a possible target for the treatment of Oc.

Systematic Investigation of the Diagnostic and Prognostic Impact of LINC01087 in Human Cancers

“…In more detail, LINC01087 seemed to interfere with 2 miRNAs targeting the messenger of C8orf37 (namely has-miR-644a and has-miR-7-5p), EFNA5 (hsa-miR-1305, hsa-miR-92a-3p), HOOK3 (hsa-miR-4505, hsa-miR-181a-5p), MYOZ3 (hsa-miR-7975, hsa-miR-197-3p), and PCP4L1 (hsa-miR-4505, hsa-miR-423-5p), with 3 miRNAs targeting the mRNAs of SLC2A3 (hsa-miR-606, hsa-miR-34a-5p, hsa-miR-98-5p) and SNRPA1 (hsa-miR-3174, hsa-miR-34a-5p, hsa-miR-98-5p), and 4 miRNAs interfering with the transcripts of IQCG (hsa-miR-3671, hsa-miR-181a-5p, hsa-miR-181b-5p, hsa-miR-181d-5p), PLAG1 (hsa-miR-569, hsa-miR-181a-5p, hsa-miR-181b-5p, hsa-miR-98-5p), and POLI (hsa-miR-4255, hsa-miR-19a-3p, hsa-miR-19b-3p, hsa-miR-92a-3p). Interestingly, most of these mRNAs and miRNAs have been connected to tumor suppressive and/or oncogenic functions in multiple cancers [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ].…”

“…Some mRNAs and miRNAs of the established LINC01087 network are related to malignant disease [ 51 , 52 , 53 ]. For instance, miR-3174 (targeting SNRPA1 mRNA) exhibits oncogenic activity, whereas miR-34a-5p and hsa-miR-644a (targeting SLC2A3 and C8orf37 mRNAs, respectively) possess tumor-suppressive properties [ 60 , 61 , 77 , 78 , 79 ].…”

Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples

“…However, PLAG1 is a zinc-finger transcription factor that has been described as an oncogene in other type of tumors. Previous studies demonstrated that it could promote anoikis resistance and tumor metastasis in lung cancer [ 94 ], and its silencing also promoted cell-chemosensitivity in ovarian cancer [ 95 ]. The oncogenic capability of PLAG1 seemed to be mediated, at least partly, by the IGF-II-mitogenic signaling pathway [ 95 , 96 ].…”

“…Previous studies demonstrated that it could promote anoikis resistance and tumor metastasis in lung cancer [ 94 ], and its silencing also promoted cell-chemosensitivity in ovarian cancer [ 95 ]. The oncogenic capability of PLAG1 seemed to be mediated, at least partly, by the IGF-II-mitogenic signaling pathway [ 95 , 96 ]. Interestingly, JAKMIP2 (Janus Kinase and Microtubule Interacting Protein 2) and VTI1b (Vesicle Transport Through Interaction With T-SNAREs 1B) have been linked to vesicle transport.…”

Important players in carcinogenesis as potential targets in cancer therapy: an update

“…This factor is one of the elements of the complex signaling system, which consists of insulin; two isoforms of its receptor, IR-A, IR-B; insulin-like growth factors, IGF-1, IGF-2; their receptors, IGF-1R, IGF-2R; and two subfamilies of proteins binding this factor, IGFBPs, IGF2BPs. Studies conducted on various types of tumor cells have shown IGF-2 overexpression and increased IGF-1R receptor prevalence [121][122][123]. This fact is associated with a worse prognosis, shorter survival, and the development of resistance to chemotherapy [124,125].…”