Evaluation of Long Non-coding RNA (LncRNA) in the Pathogenesis of Chemotherapy Resistance in Cervical Cancer: Diagnostic and Prognostic Approach

Modabber, Noushin; Mahboub, Sarah Sadat; Khoshravesh, Sahar; Karimpour, Fatemeh; Karimi, Anita; Goodarzi, Vahid

doi:10.1007/s12033-023-00909-6

Cited by 5 publications

(2 citation statements)

References 125 publications

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“…A recent study has revealed interactions between viral oncoproteins and lncRNAs [ 13 ], besides a study from our laboratory showing the interaction between HPV16 E7 oncoprotein and lncRNA HOTAIR [ 14 ]. Such findings therefore, establish the significant functional roles of lncRNAs in CaCx pathogenesis [ 12 ]. Hence, exploration of lncRNAs-mRNAs-viral oncoprotein axes merit attention, with the potential of novel biomarker or target discovery for the HPV-driven CaCx cases.…”

Section: Introductionmentioning

confidence: 80%

“…Recent studies have shown that lncRNAs can epigenetically or post-transcriptionally regulate coding gene transcription, involving alternative splicing mechanisms [ 9 ]. Current evidences show that long noncoding RNAs (lncRNAs) play an important regulatory role in cancer pathogenesis, including progression, response to therapy, and prognosis [ 10 , 11 ], through their influence on many cancer-associated hallmarks [ 12 ]. A recent study has revealed interactions between viral oncoproteins and lncRNAs [ 13 ], besides a study from our laboratory showing the interaction between HPV16 E7 oncoprotein and lncRNA HOTAIR [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2

Sinha,

Ghosh,

Ghosh

et al. 2024

Clin Epigenet

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Background MAL (T-lymphocyte maturation-associated protein) is highly downregulated in most cancers, including cervical cancer (CaCx), attributable to promoter hypermethylation. Long noncoding RNA genes (lncGs) play pivotal roles in CaCx pathogenesis, by interacting with human papillomavirus (HPV)-encoded oncoproteins, and epigenetically regulating coding gene expression. Hence, we attempted to decipher the impact and underlying mechanisms of MAL downregulation in HPV16-related CaCx pathogenesis, by interrogating the interactive roles of MAL antisense lncRNA AC103563.8, E7 oncoprotein and PRC2 complex protein, EZH2. Results Employing strand-specific RNA-sequencing, we confirmed the downregulated expression of MAL in association with poor overall survival of CaCx patients bearing HPV16, along with its antisense long noncoding RNA (lncRNA) AC103563.8. The strength of positive correlation between MAL and AC103563.8 was significantly high among patients compared to normal individuals. While downregulated expression of MAL was significantly associated with poor overall survival of CaCx patients bearing HPV16, AC103563.8 did not reveal any such association. We confirmed the enrichment of chromatin suppressive mark, H3K27me3 at MAL promoter, using ChIP-qPCR in HPV16-positive SiHa cells. Subsequent E7 knockdown in such cells significantly increased MAL expression, concomitant with decreased EZH2 expression and H3K27me3 marks at MAL promoter. In silico analysis revealed that both E7 and EZH2 bear the potential of interacting with AC103563.8, at the same binding domain. RNA immunoprecipitation with anti-EZH2 and anti-E7 antibodies, respectively, and subsequent quantitative PCR analysis in E7-silenced and unperturbed SiHa cells confirmed the interaction of AC103563.8 with EZH2 and E7, respectively. Apparently, AC103563.8 seems to preclude EZH2 and bind with E7, failing to block EZH2 function in patients. Thereby, enhanced EZH2 expression in the presence of E7 could potentially inactivate the MAL promoter through H3K27me3 marks, corroborating our previous results of MAL expression downregulation in patients. Conclusion AC103563.8-E7-EZH2 axis, therefore, appears to crucially regulate the expression of MAL, through chromatin inactivation in HPV16-CaCx pathogenesis, warranting therapeutic strategy development.

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Section: Introductionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2

Sinha,

Ghosh,

Ghosh

et al. 2024

Clin Epigenet

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FNDC5 inhibits malignant growth of human cervical cancer cells via restraining PI3K/AKT pathway

Li,

Wang,

et al. 2024

Journal Cellular Physiology

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Cervical cancer (CxCa) is the fourth most frequent cancer in women. This study aimed to determine the role and underlying mechanism of fibronectin type III domain‐containing protein 5 (FNDC5) in inhibiting CxCa growth. Experiments were performed in human CxCa tissues, human CxCa cell lines (HeLa and SiHa), and xenograft mouse model established by subcutaneous injection of SiHa cells in nude mice. Bioinformatics analysis showed that CxCa patients with high FNDC5 levels have a longer overall survival period. FNDC5 expression was increased in human CxCa tissues, HeLa and SiHa cells. FNDC5 overexpression or FNDC5 protein not only inhibited proliferation, but also restrained invasion and migration of HeLa and SiHa cells. The effects of FNDC5 were prevented by inhibiting integrin with cilengitide, activating PI3K with recilisib or activating Akt with SC79. FNDC5 inhibited the phosphorylation of PI3K and Akt, which was attenuated by recilisib. PI3K inhibitor LY294002 showed similar effects to FNDC5 in HeLa and SiHa cells. Intravenous injection of FNDC5 (20 μg/day) for 14 days inhibited the tumor growth, and reduced the proliferation marker Ki67 expression and the Akt phosphorylation in the CxCa xenograft mouse model. These results indicate that FNDC5 inhibits the malignant phenotype of CxCa cells through restraining PI3K/Akt signaling. Upregulation of FNDC5 may play a beneficial role in retarding the tumor growth of CxCa.

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piR-823 tale as emerging cancer-hallmark molecular marker in different cancer types: a step-toward ncRNA-precision

Shaker,

Sanad,

Elghazaly

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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PIWI-interacting RNAs (piRNAs) have received a lot of attention for their functions in cancer research. This class of short non-coding RNAs (ncRNA) has roles in genomic stability, chromatin remodeling, messenger RNA (mRNA) integrity, and genome structure. We summarized the mechanisms underlying the biogenesis and regulatory molecular functions of piRNAs. Among all piRNAs studied in cancer, this review offers a comprehensive analysis of the emerging roles of piR-823 in various types of cancer, including colorectal, gastric, liver, breast, and renal cancers, as well as multiple myeloma. piR-823 has emerged as a crucial modulator of various cancer hallmarks through regulating multiple pathways. In the current review, we analyzed several databases and conducted an extensive literature search to explore the influence of piR-823 in carcinogenesis in addition to describing the potential application of piR-823 as prognostic and diagnostic markers as well as the therapeutic potential toward ncRNA precision.

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Evaluation of Long Non-coding RNA (LncRNA) in the Pathogenesis of Chemotherapy Resistance in Cervical Cancer: Diagnostic and Prognostic Approach

Cited by 5 publications

References 125 publications

MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2

MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2

FNDC5 inhibits malignant growth of human cervical cancer cells via restraining PI3K/AKT pathway

piR-823 tale as emerging cancer-hallmark molecular marker in different cancer types: a step-toward ncRNA-precision

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