<i>SOX2</i> mediates cisplatin resistance in small‐cell lung cancer with downregulated expression of hsa‐miR‐340‐5p

Cui, Fei; Hao, Zhexue; Li, Jin; Zhang, Yalei; Li, Xukai; He, Jianxing

doi:10.1002/mgg3.1195

Cited by 17 publications

(11 citation statements)

References 46 publications

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“…Additionally, studies found that SOX2 regulates the stem cell properties and drug resistance of cancer cells [10], which was consistent with our previous ndings for the role of SOX2 in NSCLC A549/CDDP cells [28].The mechanisms of resistance to cisplatin among different cell types are different and complicated [19]. Notably, SOX2 is involved in cisplatin resistance events [19,29,30]. Emerging downstream targets regulating SOX2, such as cyclin D1, Nanog, SKIL, and PI3K, have been found [5,31,32].…”

Section: Discussionsupporting

confidence: 88%

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling

Chen

Zhou

et al. 2021

Preprint

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Objective SOX2 is related to drug resistance in many types of cancer, including lung cancer. Herein, we investigated the role of SOX2 and its regulatory signaling in cisplatin-treated non-small-cell lung cancer (NSCLC). Methods The effects of SOX2 on cell viability, proliferation, and apoptosis were evaluated in vitro. Western blotting, real-time quantitative PCR (qPCR), immunohistochemistry (IHC), and luciferase reporter assays were used to investigate the underlying mechanism. Kaplan-Meier survival analysis and the log-rank test were used to assess the relationship between SOX2 expression and patient survival. Results A549/CDDP cells had marked resistance to cisplatin and stronger colony formation ability than A549 cells. The expression of SOX2 protein or mRNA in A549/CDDP was higher than that in A549. Knockdown of SOX2 in A549/CDDP induced apoptosis by inhibiting colony formation and decreasing viability, but overexpression of SOX2 reversed these effects. Interestingly, Genomatix software predicted that the APE1 promoter has some SOX2 binding sites, while the SOX2 promoter has no APE1 binding sites. Furthermore, luciferase reporter assays proved that SOX2 could bind the promoter of APE1 in 293T cells. We further verified that SOX2 expression was not affected by shAPE1 in A549/CDDP. As expected, colony formation was obviously inhibited and apoptosis was strongly enhanced in A549/CDDP treated with SOX2 siSOX2 alone or combined with CDDP compared with control cells. Meaningfully, patients with high expression of SOX2 survived longer than those with low expression of SOX2. Conclusion siSOX2 overcomes cisplatin resistance by regulating APE1 signaling, providing a new target for overcoming cisplatin resistance in NSCLC.

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Section: Discussionsupporting

confidence: 88%

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling

Chen

Zhou

et al. 2021

Preprint

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“…The mechanisms of resistance to cisplatin among different cell types are different and complicated [ 20 ]. Notably, SOX2 is involved in cisplatin resistance events [ 20 , 30 , 31 ]. Emerging downstream targets regulating SOX2, such as cyclin D1, Nanog, SKIL, and PI3K, have been found [ 5 , 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling

Chen

Zhou

et al. 2022

Med Oncol

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SOX2 is related to drug resistance in many types of cancer, including lung cancer. Herein, we investigated the role of SOX2 and its regulatory signaling in cisplatin-treated non-small-cell lung cancer (NSCLC). The effects of SOX2 on cell viability, proliferation, and apoptosis were evaluated in vitro. Western blotting, real-time quantitative PCR, immunohistochemistry, and luciferase reporter assays were used to investigate the underlying mechanism. Kaplan–Meier survival analysis and the log-rank test were used to assess the relationship between SOX2 expression and patient survival. A549/CDDP cells had marked resistance to cisplatin and stronger colony formation ability than A549 cells. The expression of SOX2 protein or mRNA in A549/CDDP was higher than that in A549. Knockdown of SOX2 in A549/CDDP-induced apoptosis by inhibiting colony formation and decreasing viability, but overexpression of SOX2 reversed these effects. Interestingly, Genomatix software predicted that the APE1 promoter has some SOX2 binding sites, while the SOX2 promoter has no APE1 binding sites. Furthermore, luciferase reporter assays proved that SOX2 could bind the promoter of APE1 in 293T cells. We further verified that SOX2 expression was not affected by shAPE1 in A549/CDDP. As expected, colony formation was obviously inhibited and apoptosis was strongly enhanced in A549/CDDP treated with SOX2 siSOX2 alone or combined with CDDP compared with control cells. Meaningfully, patients with low expression of SOX2, and even including its regulating APE1, survived longer than those with high expression of SOX2, and APE1. siSOX2 overcomes cisplatin resistance by regulating APE1 signaling, providing a new target for overcoming cisplatin resistance in NSCLC.

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“…Accordingly, identifying pivotal genes and understanding the molecular pathways involved in GC progression and chemoresistance is important for developing therapeutic intervention strategies against GC. Recent studies have also revealed that SOX2 makes a contribution to chemoresistance and promotes EMT in different types of human cancers ( Cui et al, 2020 ; Zhu et al, 2021a ; Zhu et al, 2021b ). However, the underlying molecular regulatory mechanism of this event remains to be further elucidated.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg3 Alleviates Cisplatin Resistance of Gastric Cancer Cells Through Inhibiting SOX2 and the PI3K/Akt/mTOR Signaling Axis by Up-Regulating miR-429

Wang

Geng

et al. 2022

Front. Genet.

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Platinum-based cytotoxic chemotherapy is considered the standard treatment for advanced gastric cancer (GC). However, cisplatin chemoresistance often occurs with the mechanisms being not well clarified, which results in the cancer recurrence and poor survival. Ginsenoside Rg3, isolated from the Chinese Herb Panax Ginseng, is recognized as an anti-cancer agent. Herein, we aimed to reveal whether Ginsenoside Rg3 alleviates cisplatin resistance and sensitizes GC cells to cisplatin-induced apoptosis, and draw out the underlying molecular mechanism in cisplatin-resistant GC cells. The lower expression of miR-429 was found in AGSR-CDDP cells; it was also in association with cisplatin-resistance in GC cells and expression of which was restored following Ginsenoside Rg3 treatment. We also demonstrated that miR-429 made a contribution toward chemosensitivity in GC cells partly through SOX2 regulation. SOX2 was found to contribute to developing platinum resistance and was an authentic target for miR-429 in AGSR-CDDP cells. Importantly, enforced expression of SOX2 with a pcDNA3-SOX2 construct lacking the 3′-UTR miRNA binding site diminished the cytotoxic effects of miR-429 in AGSR-CDDP cells. We demonstrated that Ginsenoside Rg3 enhanced chemosensitivity in AGSR-CDDP GC cells, at least in part, through up-regulating miR-429, thereby targeting SOX2 and modulating downstream PI3K/AKT/mTOR signaling. Ginsenoside Rg3 was also found to regulate apoptosis-related genes via miR-429 in cisplatin-resistant GC cells. Ginsenoside Rg3 treatment significantly suppressed the migration rate of AGSR-CDDP GC cells, while following transfection with anti-miR-429, the anti-migratory effects of Ginsenoside Rg3 was partially abolished. This data suggested that Ginsenoside Rg3 may impede the chemoresistance and migration of GC cells mainly mediated through miR-429. We concluded that miR-429-regulated SOX2 expression was one of the main mechanisms by which Ginsenoside Rg3 dramatically promoted its anticancer effects on cisplatin-resistant GC cells. We also underscored a supporting model in which miR-429 adjusted PI3K/AKT/mTOR signaling by regulating SOX2 in cisplatin-resistant GC cells.

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SOX2 mediates cisplatin resistance in small‐cell lung cancer with downregulated expression of hsa‐miR‐340‐5p

Cited by 17 publications

References 46 publications

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling

Ginsenoside Rg3 Alleviates Cisplatin Resistance of Gastric Cancer Cells Through Inhibiting SOX2 and the PI3K/Akt/mTOR Signaling Axis by Up-Regulating miR-429

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