. 2020 Jun 19;5:102. doi: 10.1038/s41392-020-0194-y

Table 5.

ncRNAs influence TIE via regulating immune checkpoint molecules

Target genes	ncRNAs	Function	Type of cancer	Refs.
CTLA-4
	miR-138 and miR-155	Downregulate CTLA-4 on tumor-infiltrating T cells directly, promote the recognition and killing of tumor cells by the immune system	Mouse gliomas, Mouse melanoma	^151,152
PD-L1
	miR-424, 16, 195, 34a, 15a, 15b, 16, 193a-3p, 873, 497-5p, 570, 152, 142-5p, 138-5p and lncRNA NKX2-1-AS1	Downregulate PD-L1 on tumor cells directly, inhibit immunosuppression and preventing TIE	Ovarian cancer, Prostate cancer, AML, Malignant pleural mesothelioma, Breast cancer, Clear cell renal cell carcinoma, Gastric cancer, Pancreatic cancer, Colorectal cancer, Lung carcinoma	^{159–162,164,174,446–450}
	circRNA CDR1-AS	Upregulates PD-L1 on tumor cells directly, promotes immunosuppression and TIE	Colon cancer	¹⁷³
	lncRNA SNHG14	Upregulates PD-L1 by SNHG14/miR-5590-3p/ZEB1 positive feedback loop, promotes immunosuppression and TIE	Large B cell lymphoma	¹⁷²
	miR-24-2 and miR-200c	Downregulate PD-L1 by inhibiting the IFN-γ in IFN-γ signaling pathway, inhibit immunosuppression and TIE	Cervical cancer	¹⁶⁵
	miR-186	Downregulates PD-L1 by inhibiting SHP-2 in IFN-γ signaling pathway, inhibits immunosuppression and TIE	Oral squamous cell carcinoma	¹⁶⁶
	miR-4510	Downregulates PD-L1 by inhibiting RAF1 in IFN-γ signaling pathway, inhibits immunosuppression and TIE	HCC	⁴⁵¹
	miR-101	Downregulates PD-L1 by inhibiting MEK1 in IFN-γ signaling pathway, inhibits immunosuppression and TIE	Nasopharyngeal carcinoma	⁴⁵²
	miR-27a, 145, 150, 223 and 200c	Downregulate PD-L1 by inhibiting STAT1 in the IFN-γ signaling pathway, inhibit immunosuppression and TIE	Cervical cancer, Colon cancer, Adult T cell leukemia/lymphoma, Cervical cancer	^165,167,453
	miR-383	Downregulates PD-L1 by inhibiting IRF1 in the IFN-γ signaling pathway, inhibit immunosuppression and TIE	Testicular embryonal carcinoma	⁴⁵⁴
	miR-101, 181b and 490-5p	Downregulate PD-L1 by inhibiting c-FOS in the IFN-γ signaling pathway, inhibit immunosuppression and TIE	Osteosarcoma, Glioma, Bladder cancer	^455–457
	miR-10a, 19a, 19b, 106b, 221, 222, 20b, 21, 130b, 92a, 26a, 205, 214, 301a and 142-5p	Upregulate PD-L1 by inhibiting PTEN in PTEN/PI3K/AKT/mTOR pathway, promote immunosuppression and TIE	NSCLC, Gastric cancer, Colorectal cancer, Lung cancer, Nasopharyngeal carcinoma, Ovarian cancer, Breast cancer, NSCLC	^{168,169,458–466}
	miR-100, 101, 199a-3p and 497	Upregulate PD-L1 by downregulating mTOR in PTEN/PI3K/AKT/mTOR pathway, promote immunosuppression and TIE	Bladder cancer, Osteosarcoma cell, Endometrial cancer cell, Ovarian cancer	^{170,467–469}
	miR-216a	Upregulates PD-L1 by downregulating EIF4B in PTEN/PI3K/AKT/mTOR pathway, promotes immunosuppression and TIE	NSCLC	¹⁷¹
PD-1
	miR-28, 138 and 4717	Downregulate PD-1 directly on tumor-infiltrating T cells, promotes the activity and function of T cells and inhibit TIE	Mouse melanoma, Mouse glioma, Chronic HBV	^151,179,470
	ncRNA AFAP1-AS1	Up- regulates PD-1 expression on tumor-infiltrating lymphocytes, inhibits the activity and function of lymphocytes and promotes TIE	Nasopharyngeal carcinoma	¹⁸¹
TIM-3
	miR-28	Reduces T cell exhaustion and increasing TNF-α and IL-2 secretion by downregulating TIM-3 directly, thereby inhibiting TIE	Melanoma	¹⁷⁹
	lncRNA Tim3	Exacerbates CD8⁺ T cell exhaustion by specifically binding to TIM-3, thereby promoting TIE	HCC	¹⁸⁴
BTLA
	miR-28 and miR-155	Downregulate BTLA directly and enhance antitumor immune response and inhibit TIE	Melanoma, CD4+ T cell	^179,186