Medroxyprogesterone acetate causes the alterations of endoplasmic reticulum related mRNAs and lncRNAs in endometrial cancer cells

Abstract

BackgroundProgestin is effective to promote endometrial cancer (EC) cells apoptosis, however, continuous progestin administration causes low level of progestin receptor B (PRB), further resulting in progestin resistance. Here, we performed microarray analysis on Ishikawa cells (PRB+) treated with medroxyprogesterone acetate (MPA) to explore the molecular mechanism underlying the inhibitory influence of MPA on PRB+ EC cells.MethodsMicroarray analysis was performed by using Ishikawa cells (PRB+) treated with MPA. Differentially expressed mRNA and long noncoding RNAs (lncRNAs) were identified. Furthermore, the functions of these mRNAs and lncRNAs were predicted by functional enrichment analysis. QRT-PCR was further performed to verify the microarray data.ResultsA total of 358 differentially expressed genes and 292 lncRNAs were identified in Ishikawa cells (PRB+) treated with MPA. QRT-PCR verified these data. Functional enrichment analysis identified endoplasmic reticulum (ER) stress as the key pathway involved in the inhibitory effect of MPA on EC cells. And the ER stress apoptotic molecule CHOP and ER stress related molecule HERPUD1 were both highly expressed in Ishikawa cells (PRB+) treated with MPA. Co-expression analysis showed lnc-CETP-3 was highly correlated with CHOP and HERPUD1, suggesting it might participate in ER stress pathway-related EC cell apoptosis caused by MPA. In addition, compared with untreated cells, lnc-CETP-3, CHOP and HERPUD1 were significantly up-regulated in Ishikawa cells (PRB+) treated with MPA, whereas they have no statistical significance in KLE cells (PRB-).ConclusionsMPA may activate ER stress by progesterone-PRB pathway to up-regulate CHOP expression, which may be one of the molecular mechanisms underlying the inhibitory effect of MPA on EC cells with PRB+. Lnc-CETP-3 might be involved in this process. These findings may provide therapeutic targets for EC patients with PRB-, and resistance-related targets to increase the sensitivity of MPA on EC cells.

Effects of homocysteine-induced endoplasmic reticulum protein on endoplasmic reticulum stress, autophagy, and neuronal apoptosis following intracerebral hemorrhage

“…To further study HERP localization and expression in neurons after ICH, immunofluorescent staining was performed with cells specific marker: NeuN (a marker of neuron). As described previously ( Cao et al, 2019 ), we found that HERP co-located with neurons in the cytoplasm. As shown in Fig.…”

“…Homocysteine-induced endoplasmic reticulum protein (HERP), a 54 kD transmembrane protein, is an early stress response protein encoded by homocysteine-inducible and ER-stress-inducible, ubiquitin-like domain member 1 (Herpud1) gene. It is dramatically induced by ER stress in a variety of pathological conditions, including ICH ( Cao et al, 2019 ; George et al, 2018 ; Kokame et al, 2000 ; Maeda et al, 2018 ). HERP also plays a significant role in ER-associated protein degradation (ERAD), which is the principal mechanism of protein degradation that misfolding unfortunately.…”

Development of a nine‑lncRNA signature as a novel prognostic marker of estrogen receptor‑negative breast cancer

“…In recent years, a number of studies have demonstrated that dysregulated lncRNAs play an important role in the carcinogenesis, development and metastasis of different types of tumor (33)(34)(35). A number of lncRNAs have been reported to be associated with the recurrence, metastasis and resistance to adjuvant therapy of patients with BC (36,37).…”

Hsa-circ-0001860 promotes Smad7 to enhance MPA resistance in endometrial cancer via miR-520h

“…For example, HOTAIR and LSD1 collaboratively repress PRB expression and thus reduce progesterone sensitivity in endometrial carcinoma cells 31 . CHOP and Lnc-CETP-3 might be involved in progesterone-PRB pathway to activate ER stress and provide therapeutic targets for EC patients with negative PRB expression 32 .…”