Emerging role of long non-coding RNAs in cisplatin resistance

Figures & data

Figure 1 Molecular mechanisms of cisplatin resistance.

Notes: Multiple cellular alterations in cancer cells, including cell cycle, apoptosis, autophagy, stemness, intracellular detoxification, and drug influx/efflux, contribute to cisplatin chemoresistance through genetic and/or epigenetic regulation of multiple signaling pathways. Some major genetic and epigenetic factors are illustrated in the figure (see text for detailed discussion).
Abbreviations: ALDH1, aldehyde dehydrogenase 1 family member A1; ATG7, autophagy associated gene; BRCA2, breast cancer susceptibility proteins 2; CTR1, copper transporter 1; ERCC1, excision repair cross-complementing rodent repair deficiency, complementation group 1; GSH, glutathione; GST, glutathione S-transferase; HR, homologous recombination; MMR, mismatch repair; MRP, multidrug-resistant-associated protein; NER, nucleotide excision repair; γ-GCS, γ-glutamylcysteine synthetase.

Table 1 Predictive lncRNAs involved in response to cisplatin

lncRNAs	Role in response	Targets	Mechanisms	Cancers	Ref
AC023115.3	S	miR-26a/GSK3β	ceRNA	Glioblastoma	^Citation76
AK022798	R	MRP1, P-gp	N/A	Gastric cancer	^Citation39
AK126698	R	Wnt/β-catenin	N/A	NSCLC	^Citation69
ANRIL	R	MDR1, MRP1	N/A	Gastric cancer	^Citation41
ANRIL	R	let-7a	N/A	Nasopharyngeal carcinoma	^Citation50
CASC2	S	miR-21/PTEN	ceRNA	Cervical cancer	^Citation80
ENST000457645	S	Bax, caspase-3	N/A	Ovarian cancer	^Citation59
GAS5	S	miR-21/PI3K/Akt	ceRNA	Cervical cancer	^Citation83
GAS5	S	miR-21/PTEN	ceRNA	NSCLC	^Citation81
HOTAIR	R	NF-κB	By decreasing Iκ-Bα	Ovarian cancer	^Citation48
HOTAIR	R	p21^Waf1/Cip1	N/A	Lung adenocarcinoma	^Citation49
HOTAIR	R	Beclin-1, MDR, and P-gp	N/A	Endometrial cancer	^Citation74
HOTAIR	R	Klf4	N/A	NSCLC	^Citation78
HOTTIP	R	Wnt/β-catenin	N/A	Osteosarcoma	^Citation71
H19	R	NRF2	N/A	Ovarian cancer	^Citation46
H19	R	FAS, BAK, BAX	N/A	Lung adenocarcinoma	^Citation58
LINC00161	S	miR-645/IFIT2	ceRNA	Osteosarcoma	^Citation79
MEG3	S	p53, β-catenin, survivin, Bcl-xl	N/A	Lung cancer	^Citation53, ^Citation54
MEG3	S	miR-214	N/A	Ovarian cancer	^Citation63
MEG3	S	miR-21-5p/SOX7	ceRNA	NSCLC	^Citation82
NEAT1	S	CTR1	ceRNA	Lung cancer	^Citation43
PDAM	S	p53, BCL2L1	N/A	Glioma	^Citation51
PVT1	R	MDR1, MRP, mTOR, HIF-1a	N/A	Gastric cancer	^Citation40
PVT1	R	TGF-β1, p-Smad4, caspase-3	N/A	Ovarian cancer	^Citation60
ROR	R	p53	N/A	Nasopharyngeal carcinoma	^Citation52
SFTA1P	S	hnRNP-U-/ADD45A	N/A	LSCC	^Citation64
TRPM2-AS	R	p53-p66^shc	N/A	NSCLC	^Citation56
UCA1	R	miR-196a	Affecting transcription by activating CREB	Bladder cancer	^Citation61
UCA1	R	Caspase-3, CDK2, surviving, p21	N/A	Cervical cancer	^Citation62
UCA1	R	Wnt/β-catenin	N/A	Bladder cancer	^Citation70
XIST	R	miR-17/ATG7	ceRNA	NSCLC	^Citation75

Abbreviations: ABCB1, ATP-binding cassette subfamily B member 1; ABCC1, ATP-binding cassette subfamily C member 1; ABCG2, ATP-binding cassette subfamily G member 2; ceRNA, competing endogenous RNA; CREB, cAMP response element-binding protein; CTR1, copper transporter 1; lncRNAs, long non-coding RNAs; LSCC, lung squamous cell carcinoma; MDR1, multidrug-resistant protein; MRP1, multidrug-resistant-associated protein 1; N/A, not available; NEAT1, nuclear-enriched abundant transcript 1; NSCLC, non-small-cell lung cancer; P-gp, P-glycoprotein; R, resistance; Ref, reference; S, sensitivity.

Figure 2 Role of lncRNAs in cisplatin resistance.

Notes: lncRNAs that regulate drug efflux, drug uptake, apoptosis, DDR, cell cycle arrest, and autophagy of cancer cells are implicated in cisplatin resistance. Gray arrows indicate inhibition and black arrows indicate activation.
Abbreviations: DDR, DNA damage response; lncRNAs, long non-coding RNAs; MDR1, multidrug-resistant protein; MRP1, multidrug-resistant-associated protein 1.

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