Page 97 - Read Online

Page 8 of 20 Zhang et al. Cancer Drug Resist 2024;7:34 https://dx.doi.org/10.20517/cdr.2024.59

[116]
interaction with pEZH2-S21, which contributes to resistance against both CDDP and cetuximab .
Another study demonstrated that VN1R5 upregulates lncRNA POP1-1, leading to the promotion of CDDP
[117]
resistance in HNSCC through its interaction with MCM5 . LSCC represents a highly prevalent subtype of
laryngeal cancer, ranking second in incidence among respiratory tumors. Chemotherapy is regarded as the
established first-line treatment for patients with advanced LSCC . A study reported that the activation of
[118]
[119]
the STAT3 signaling pathway by lncRNA FOXD2-AS1 enhances CDDP resistance in LSCC . OSCC is the
prevailing malignant tumor of the oral mucosa, with 57.5% of global oral cancer cases being reported in
Asia, particularly in India . FOXD1 upregulates the expression of lncRNA CYTOR, promoting EMT and
[120]
conferring CDDP resistance in OSCC . Additionally, it has been reported that in OSCC, HOXA11-AS
[76]
upregulates the expression of NQO1 by sponging microRNA-494 while downregulating the expression of
NQO2. This regulatory mechanism promotes tumor progression and contributes to drug resistance .
[56]
TSCC is characterized by a significant upregulation in the expression of miRNA processing-related lncRNA
(MPRL), which disrupts pre-miRNA processing. This disruption promotes mitochondrial fission and
enhances CDDP chemosensitivity in TSCC . TC is a prevalent endocrine malignancy, comprising
[121]
approximately 1% of all malignant tumors. Moreover, its incidence is consistently rising on a global
scale . Papillary thyroid cancer (PTC) is the most common histological subtype of TC, accounting for
[122]
89.1% of cases. Studies have shown that the LncRNA Glycolysis-Associated Regulator of LDHA post-
transcriptional modification (GLTC) is significantly upregulated in PTC tissues and correlates with more
extensive distant metastasis, increased tumor size, and poorer prognosis. GLTC facilitates the succinylation-
dependent activation of LDHA, thus promoting resistance to radioiodine therapy. These findings provide a
theoretical foundation for considering the GLTC-LDHA pathway a potential target for therapeutic
[123]
intervention in PTC .

Several lncRNAs have been found to have close associations with the malignant biology of tumors. In LSCC,
HCP5 exhibits high expression levels. The knockdown of HCP5 has been shown to inhibit malignant
biological functions through the regulation of miR-216a-5p/ZEB1 signaling pathway . In OSCC,
[35]
lnc-p23154 is believed to play a significant role in glut1-mediated glycolysis and promote tumor metastasis
[124]
by suppressing the transcription of miR-378a-3p . Additionally, the mitochondria-localized lncRNA
growth-arrest-specific 5 (GAS5) has been identified as a tumor suppressor that plays a critical role in
maintaining cellular energy homeostasis . The targeting of epidermal growth factor receptor (EGFR) has
[125]
proven to be an effective therapeutic strategy for the treatment of SCCs. Notably, studies have indicated that
[126]
lnc-EGFR-AS1 is involved in mediating EGFR addiction and influencing treatment responses in SCCs
[Table 3 and Figure 2].

Substantial evidence supports the dependence of cellular homeostasis on lncRNAs [125,127] . However, despite a
small fraction of the thousands of expressed lncRNAs potentially having functional roles in cancer cells, the
[128]
extent of their involvement remains inadequately studied . Further research is warranted to explore the
role of lncRNAs in various aspects concerning tumor chemotherapy, targeted therapy, and immunotherapy,
as well as their impact on the tumor microenvironment [129,130] .

circRNAs IN HNC CELL DRUG RESISTANCE
The discovery of single-stranded covalently closed circular RNA dates back to 1976, with subsequent
[131]
findings revealing their common presence in both viruses and mammals . circRNAs exhibit a diverse
range of functions, encompassing their role as protein scaffolds or miRNA sponges, and their capacity for
translation into polypeptides . The unique structure of circRNAs grants them a longer half-life compared
[132]
to linear RNA and provides resistance against RNase R degradation . Consequently, circRNAs have
[133]
garnered significant attention as reliable diagnostic and prognostic biomarkers in cancer diagnosis,
treatment, and prevention [13,16,134-137] .