miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1

Su, Wenmei; Mo, Yanli; Wu, Fenping; Guo, Kangwen; Luo, Yiping; Ye, Haiyin; Guo, Hongsheng; Li, Dongming; Yang, Zhijian

doi:10.1016/j.biopha.2016.09.027

Cited by 39 publications

(22 citation statements)

References 22 publications

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“…Earlier studies have shown that activation of NF-kB is associated with resistance to therapy and poor clinical outcome (51,52). Previous studies have suggested that overexpression of miR-135b-5p in non-small cell lung cancer and colorectal cancer can lead to chemotherapeutic resistance to cisplatin and 5-FU (19,53). Our findings indicate that high levels of miR-135b-5p promote resistance to cisplatin treatment in gastric cancer cells.…”

Section: Discussionsupporting

confidence: 60%

Helicobacter pylori‐induced miR‐135b‐5p promotes cisplatin resistance in gastric cancer

et al. 2018

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Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression of miR-135b-5p and its role in gastric cancer. We describe the overexpression of miR-135b-5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR-135b-5p is also up-regulated in gastric tumors from the trefoil factor 1-knockout mouse model. Infection with H. pylori induced the expression of miR-135b-5p in the in vitro and in vivo models. miR-135b-5p induction was mediated by NF-κB. Treatment of gastric cancer cells with TNF-α induced miR-135b-5p in a NF-κB-dependent manner. Mechanistically, we found that miR-135b-5p targets Krüppel-like factor 4 (KLF4) and binds to its 3' UTR, leading to reduced KLF4 expression. Functionally, high levels of miR-135b-5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection and miR-135b-5p-KLF4, suggesting that targeting miR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.-Shao, L., Chen, Z., Soutto, M., Zhu, S., Lu, H., Romero-Gallo, J., Peek, R., Zhang, S., El-Rifai, W. Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer.

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Section: Discussionsupporting

confidence: 60%

Helicobacter pylori‐induced miR‐135b‐5p promotes cisplatin resistance in gastric cancer

et al. 2018

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“…In breast cancer, overexpression of miR-135b-5p facilitated apoptosis and reduced chemoresistance to doxorubicin by targeting pro-oncogenic AGR2 (41). In non-small cell lung cancer, amplification of miR-135b suppressed the chemoresistance of cancer cells to cisplatin treatment by downregulating Frizzled-1 (55). However, opposite effects of miR-135b-5p in certain cancers have also been reported (56,57).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Integrin Subunit Alpha 2 by miR-135b-5p Modulates Chemoresistance in Gastric Cancer

et al. 2020

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Chemotherapy has substantially improved gastric cancer (GC) patient outcomes in the past decades. However, the development of chemotherapy resistance has become the major cause of treatment failure. Although numerous molecules have been implicated in GC chemoresistance, its pathological mechanisms are still unclear. Here, we found that integrin subunit alpha 2 (ITGA2) is upregulated in chemoresistant GC cells and that increased ITGA2 levels correlated with the poor prognosis of GC patients who received chemotherapy. ITGA2 overexpression led to elevated chemotherapy resistance and drug-induced apoptosis inhibition in GC cells. ITGA2 knockdown resulted in restored chemosensitivity and increased apoptosis in chemoresistant GC cells both in vitro and in vivo. NanoString analysis revealed a unique signature of deregulated pathway expression in GC cells after ITGA2 silencing. The MAPK/ERK pathway and epithelial-mesenchymal transition (EMT) were found to be downregulated after ITGA2 knockdown. miR-135b-5p was identified as a direct upstream regulator of ITGA2. miR-135b-5p overexpression reduced chemoresistance and induced apoptosis in GC cells and attenuated ITGA2-induced chemoresistance and antiapoptotic effects by inhibiting MAPK signaling and EMT. In conclusion, this study underscored the role and mechanism of ITGA2 in GC and suggested the novel miR-135b-5p/ITGA2 axis as an epigenetic cause of chemoresistance with diagnostic and therapeutic implications.

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“…Conversely, other studies have found opposing results, demonstrating that miR-135b inhibits metastasis in prostate cancer and reverses the chemoresistance of non-small cell lung cancer cells by targeting STAT6 and Frizzled-1 (FZd1), respectively (18,19). Moreover, miR-135b-5p has been shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production by silencing the AMP-activated protein kinase (AMPK) phosphatase, Ppm1e (20).…”

Section: Mir-135b-5p Promotes Gastric Cancer Progression By Targetingmentioning

confidence: 99%

miR-135b-5p promotes gastric cancer progression by targeting CMTM3

Huang

Sun

et al. 2017

Int J Oncol

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CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) is considered to be a tumor suppressor gene in multiple types of malignancies. Previous studies have indicated that CMTM3 suppresses metastasis and epithelial-mesenchymal transition (EMT) in gastric cancer. However, its role in gastric cancer cell proliferation has rarely been discussed. Moreover, the regulatory mechanisms of CMTM3 in gastric cancer remain unclear. In this study, RT‑qPCR and IHC were used to assess the expression of CMTM3 and miR‑135b‑5p in gastric cancer tissues and cell lines. We found that the expression of miR‑135b‑5p was negatively associated with CMTM3 in gastric cancer tissues, and we verified that miR‑135b‑5p directly targeted CMTM3 in gastric cancer cells by dual-luciferase reporter assay. CCK8 assay, Transwell assay and flow cytometric analysis were conducted to examine the functions of CMTM3 and miR‑135b‑5p in vitro. Our results demonstrated that the overexpression of CMTM3 or the suppression of miR‑135b‑5p using an inhibitor suppressed SGC‑7901 gastric cancer cell proliferation, invasion and cell cycle progression, and promoted SGC‑7901 cell apoptosis. Furthermore, a BALB/c nude mouse subcutaneous xenograft model was used to verify the function of miR‑135b‑5p and CMTM3. Our results revealed that miR‑135b‑5p inhibitor significantly suppressed SGC‑7901 cell tumorigenesis in vivo. In addition, IHC revealed that CMTM3 expression was markedly increased in tumors infected with miR‑135b‑5p inhibitor lentivirus. On the whole, the findings of the present study suggest that the overexpression of miR‑135b‑5p inhibits CMTM3 expression, and promotes gastric cancer progression and metastasis. Our findings provide a novel therapeutic target for gastric cancer.

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miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1

Cited by 39 publications

References 22 publications

Helicobacter pylori‐induced miR‐135b‐5p promotes cisplatin resistance in gastric cancer

Helicobacter pylori‐induced miR‐135b‐5p promotes cisplatin resistance in gastric cancer

Regulation of Integrin Subunit Alpha 2 by miR-135b-5p Modulates Chemoresistance in Gastric Cancer

miR-135b-5p promotes gastric cancer progression by targeting CMTM3

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