The functional role of long non-coding RNAs and their underlying mechanisms in drug resistance of non-small cell lung cancer

Abstract Background Lung cancer is one of the tumors with high morbidity and mortality among males and females worldwide. Proline-, glutamic acid-, and leucine-rich protein 1(PELP1) is an estrogen receptor coactivator and functions as a scaffolding protein. Its oncogenic signaling was involved in the progression of several cancers. However, there is little known about the role of PELP1 in the lung cancer. The aim of this study is to explore the role of PELP1 in non-small cell lung cancer. Methods The expression of PELP1 in microarrays of lung cancer tissue and correlation with clinicopathological parameters were performed. RNA interference technology was used to downregulate PELP1 expression in A549 lung cancer cells and the tumor cell’s ability of proliferation, migration, invasion was detected by Cell Count Kit-8 and trans-well essay. In addition, whole genome exon was analyzed by poly-A RNA-sequencing. Results Results showed that PELP1 is overexpressed in the lung cancer specimens and its expression correlate with histological type, smoking status, and EGFR status but no significant prognostic value. Knockdown of PELP1 inhibited cell proliferation, migration, invasion of lung cancer cells. Furthermore, silencing PELP1 in lung tumor cells promotes the sensitivity of tumor cells to the tyrosine kinase inhibitor Gefitinib. RNA-sequencing and Western-blotting found that 140 genes were up-regulated and 143 genes were down-regulated in PELP1 silenced lung adenocarcinoma cells, which mainly affected the mitogen-activated protein kinase (MAPK) signal pathway, EGFR tyrosine kinase inhibitor resistance, PPAR signaling pathway, Cytosolic DNA-sensing pathway, cytokine-cytokine receptor interaction, drug metabolism, cAMP signaling pathway, RIG-1-like receptor signaling pathway. Conclusions PELP1 plays a key role in non-small cell lung cancer proliferation, progression, and drug resistance. These results suggest that PELP1 could be a potential target for therapeutic intervention for lung cancer.

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NORAD accelerates chemo-resistance of non-small-cell lung cancer via targeting at miR-129-1-3p/SOX4 axis

Bioscience Reports ◽

10.1042/bsr20193489 ◽

2020 ◽

Vol 40 (1) ◽

Cited By ~ 3

Author(s):

Qiang Huang ◽

Shijiang Xing ◽

Aiping Peng ◽

Zhiwu Yu

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Downstream Target ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Nsclc Patients

Abstract Substantial researches indicated that long non-coding RNAs (lncRNAs) exerted profound effects on chemo-resistance in cancer treatment. Nonetheless, the role of NORAD in non-small-cell lung cancer (NSCLC) remains unclear. In the present study, we chose NSCLC cell lines H446 and A549 to explore the function of non-coding RNA activated damage (NORAD) in response to cisplatin (DDP) resistance of NSCLC. Experimental data manifested that NORAD was up-regulated in DDP-resistant NSCLC tissues and cells. NSCLC patients with high NORAD expression suffered a poor prognosis. NORAD knockdown resensitized H446/DDP and A549/DDP to DDP. Besides, NORAD acted as a molecular sponge of miR-129-1-3p. MiR-129-1-3p showed a low level of expression in DDP-resistant NSCLC tissues. Moreover, miR-129-1-3p overexpression impaired DDP resistance in H446/DDP and A549/DDP cells. SOX4 was the downstream target of miR-129-1-3p. Especially, SOX4 overexpression offset the effects of NORAD silence on H446/DDP and A549/DDP cells resistance to DDP. NORAD knockdown resensitized H446/DDP and A549/DDP to DDP in NSCLC via targeting miR-129-1-3p/SOX4 axis, offering a brand-new target for NSCLC chemo-resistance.

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Mechanisms of drug resistance mediated by long non-coding RNAs in non-small-cell lung cancer

Cancer Gene Therapy ◽

10.1038/s41417-020-00214-3 ◽

2020 ◽

Author(s):

Manuela La Montagna ◽

Lucy Ginn ◽

Michela Garofalo

Keyword(s):

Lung Cancer ◽

Drug Resistance ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Non Coding Rnas

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PELP1 Expressed in Non-Small Cell Lung Cancer and Promotes Tumor Cell Proliferation, Metastasis, and Drug Resistance Through MAPK Signaling Pathway.

10.21203/rs.3.rs-40995/v1 ◽

2020 ◽

Author(s):

Xingen Wang ◽

Weihua Ying ◽

Li Liang

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Drug Resistance ◽

Small Cell Lung Cancer ◽

Signaling Pathway ◽

Cell Lung Cancer ◽

Kinase Inhibitor ◽

Small Cell ◽

Small Cell Lung

Abstract Background Lung cancer is one of the tumors with high morbidity and mortality among males and females worldwide. Proline-, glutamic acid-, and leucine-rich protein 1(PELP1) is an estrogen receptor coactivator and functions as a scaffolding protein. Its oncogenic signaling was involved in the progression of several cancers. However, there is little known about the role of PELP1 in the lung cancer. The aim of this study is to explore the role of PELP1 in non-small cell lung cancer. Methods The expression of PELP1 in microarrays of lung cancer tissue and correlation with clinicopathological parameters were performed. RNA interference technology was used to downregulate PELP1 expression in A549 lung cancer cells and the tumor cell’s ability of proliferation, migration, invasion was detected by Cell Count Kit-8 and trans-well essay. In addition, whole genome exon was analyzed by poly-A RNA-sequencing. Results Results showed that PELP1 is overexpressed in the lung cancer specimens and its expression correlate with histological type, smoking status, and EGFR status but no significant prognostic value. Knockdown of PELP1 inhibited cell proliferation, migration, invasion of lung cancer cells. Furthermore, silencing PELP1 in lung tumor cells promotes the sensitivity of tumor cells to the tyrosine kinase inhibitor Gefitinib. RNA-sequencing and Western-blotting found that 140 genes were up-regulated and 143 genes were down-regulated in PELP1 silenced lung adenocarcinoma cells, which mainly affected the mitogen-activated protein kinase (MAPK) signal pathway, EGFR tyrosine kinase inhibitor resistance, PPAR signaling pathway, Cytosolic DNA-sensing pathway, cytokine-cytokine receptor interaction, drug metabolism, cAMP signaling pathway, RIG-1-like receptor signaling pathway. Conclusions PELP1 plays a key role in non-small cell lung cancer proliferation, progression, and drug resistance. These results suggest that PELP1 could be a potential target for therapeutic intervention for lung cancer.

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