Um e Habiba , Mussarat Rafiq , Muhammad Babar Khawar , Bismillah Nazir , Gulfam Haider , Nadia Nazir
{"title":"The multifaceted role of IL-12 in cancer","authors":"Um e Habiba , Mussarat Rafiq , Muhammad Babar Khawar , Bismillah Nazir , Gulfam Haider , Nadia Nazir","doi":"10.1016/j.adcanc.2022.100053","DOIUrl":"10.1016/j.adcanc.2022.100053","url":null,"abstract":"<div><p>Interleukin-12 is a heterodimeric cytokine having many family members IL-23, IL-27, IL-35, and recently discovered IL-39, produced by macrophages and dendritic cells. IL-12 is an effector cytokine and engages in anti-tumor and many immunotherapies as IL-12 DNA expression, Th1 helper cells, and natural killer cells. IL-12 stimulates interferon γ (INF-γ) synthesis by the activation of STAT4 which then differentiates the Th1 helper cells with the T-bet transcription, playing an important role in cancer treatment. This review focuses on the role of IL-12 family as an antitumor agent as understanding the biology and molecular mechanism of IL-12 family members is crucial for designing new therapeutic strategies against different cancers.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"5 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000272/pdfft?md5=60cd40f6bfc1a6dbd36839ba467edff9&pid=1-s2.0-S2667394022000272-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42708078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vaishali Aggarwal , Sarthak Sahoo , Vera S. Donnenberg , Priyanka Chakraborty , Mohit Kumar Jolly , Shilpa Sant
{"title":"P4HA2: A link between tumor-intrinsic hypoxia, partial EMT and collective migration","authors":"Vaishali Aggarwal , Sarthak Sahoo , Vera S. Donnenberg , Priyanka Chakraborty , Mohit Kumar Jolly , Shilpa Sant","doi":"10.1016/j.adcanc.2022.100057","DOIUrl":"10.1016/j.adcanc.2022.100057","url":null,"abstract":"<div><p>Epithelial-to-mesenchymal transition (EMT), a well-established phenomenon studied across pan-cancer types, has long been known to be a major player in driving tumor invasion and metastasis. Recent studies have highlighted the importance of partial EMT phenotypes in metastasis. Initially thought as a transitional state between epithelial and mesenchymal phenotypic states, partial EMT state is now widely recognized as a key driver of intra-tumoral heterogeneity and phenotypic plasticity, further accelerating tumor metastasis and therapeutic resistance. However, how tumor microenvironment regulates partial EMT phenotypes remains unclear. We have developed unique size-controlled three-dimensional microtumor models that recapitulate tumor-intrinsic hypoxia and the emergence of collectively migrating cells. In this study, we further interrogate these microtumor models to understand how tumor-intrinsic hypoxia regulates partial EMT and collective migration in hypoxic large microtumors fabricated from T47D breast cancer cells. We compared global gene expression profiles of hypoxic, migratory microtumors to that of non-hypoxic, non-migratory microtumors at early and late time-points. Using our microtumor models, we identified unique gene signatures for tumor-intrinsic hypoxia (early <em>versus</em> late), partial EMT and migration (pre-migratory <em>versus</em> migratory phenotype). Through differential gene expression analysis between the microtumor models with an overlap of hypoxia, partial EMT and migration signatures, we identified prolyl 4-hydroxylase subunit 2 (P4HA2), a hypoxia responsive gene, as a central regulator common to hypoxia, partial EMT and collective migration. Further, the inhibition of P4HA2 significantly blocked collective migration in hypoxic microtumors. Thus, using the integrated computational-experimental analysis, we identify the key role of P4HA2 in tumor-intrinsic hypoxia-driven partial EMT and collective migration.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"5 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/77/nihms-1836629.PMC9517480.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40390874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meng-Wei Ko , Barbara Breznik , Emanuela Senjor , Anahid Jewett
{"title":"Synthetic cannabinoid WIN 55,212–2 inhibits growth and induces cell death of oral and pancreatic stem-like/poorly differentiated tumor cells","authors":"Meng-Wei Ko , Barbara Breznik , Emanuela Senjor , Anahid Jewett","doi":"10.1016/j.adcanc.2022.100043","DOIUrl":"10.1016/j.adcanc.2022.100043","url":null,"abstract":"<div><p>We report here that synthetic cannabinoid WIN 55,212–2 inhibits tumor cell proliferation and induces cell death of oral and pancreatic tumor cells, and the effect is much more pronounced on stem-like/poorly differentiated OSCSCs and MP2 cells when compared to well-differentiated OSCCs, and PL-12 tumor cells. In addition, WIN 55,212-2 decreases cell surface expression of CD44, CD54, MHC class I and PD-L1 on oral and pancreatic tumor cells with the exception of PD-L1 expression on well-differentiated PL-12 pancreatic tumor cells which exhibits an increase in the expression rather than a decrease. Overall, we demonstrate that WIN 55,212-2 has an increased targeting activity against cancer stem cells/poorly differentiated oral and pancreatic tumor cells when compared to well-differentiated tumor cells, and furthermore, such differences in function do not correlate with the levels of CB1 and CB2 receptor expression on tumor cells, suggesting it's function either through post-receptor mediated activation and/or yet-to-be identified novel receptors. Intraperitoneal (IP) delivery of WIN 55-212-2 in humanized BLT mice is found to impart an activating potential for NK cells demonstrating increased NK cell mediated cytotoxicity and secretion of IFN-γ in our preliminary experiments. These results not only suggest a direct targeting of CSCs/poorly differentiated tumors by WIN 55-212-2 but also by indirect targeting of such tumors through the activation and increased functions of NK cells.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"5 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266739402200017X/pdfft?md5=10e396cf5272a210b1edee74f91026cd&pid=1-s2.0-S266739402200017X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45243472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cellular landscaping of exosomal miRNAs in cancer metastasis: From chemoresistance to prognostic markers","authors":"Rahul Bhattacharjee , Priya Mitra , Nitin Gupta , Sony Sharma , Vipendra Kumar Singh , Nobendu Mukerjee , Archna Dhasmana , Rohit Gundamaraju","doi":"10.1016/j.adcanc.2022.100050","DOIUrl":"10.1016/j.adcanc.2022.100050","url":null,"abstract":"<div><p>Exosomes are cargos facilitating the transport of miRNAs across cancer cells. Exosomal miRNA has been an area of interest in recent times due to their triple role in cancer proliferation. The current review discusses the triple role of exosomal miRNAs and proposes its application in diagnosis as a prognostic marker. Exosomal miRNAs are miRNAs found inside the exosomal structure of 30–150 nm of an extracellular vesicle. The synthesis and biogenesis of these exosomal miRNA involve an endosomal sorting complex required for transport which releases miRNAs and relevant proteins to cause tumor heterogeneity, drug resistance, and cancer metastasis. Herein, we have highlighted the role of exosomal miRNAs in both drug resistance and cancer metastasis. Additionally, we have elucidated the impact of exosomal miRNAs upon host immunity, which will provide us with the idea of host immune rejection. Furthermore, we have elaborated the clinical importance of exosomal miRNAs as a prognostic marker.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"5 ","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000247/pdfft?md5=9af9d4ecb2f30ec5c2c8acee6130fc00&pid=1-s2.0-S2667394022000247-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42829582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intervention on lactate in cancer: A promising approach for the development of cancer therapeutics","authors":"Dolly Sharma , Mamta Singh , Rajat Gupta , Vivek Kumar , Vinit Kumar , Reshma Rani","doi":"10.1016/j.adcanc.2022.100058","DOIUrl":"10.1016/j.adcanc.2022.100058","url":null,"abstract":"<div><p>Lactate, the main product of tumor glycolysis is considered one of the most crucial metabolites in the tumor microenvironment. The reprogrammed cancer cell metabolism is closely associated with the enhanced rate of tumor glycolysis leading to excess lactate production concomitant with increased extracellular acidification. This decline in pH in the vicinity of cancer cells is largely attributed to reprogrammed tumor glycolysis (Warburg effect). Substantial literature data to date suggest that lactate is not merely a waste product of tumor glycolysis, albeit serves as the main fuel to meet the anabolic requirements of cancer cells. Lactate plays a critical role in tumor growth, migration and invasion, tumor metastasis, tumor microenvironment and immune modulation. This review summarizes the current knowledge about the role of lactate in tumor glycolysis, its fate and transporters, lactate shuttle, and metabolic symbiosis. It also condenses the role of lactate in the tumor microenvironment and immune invasion and the development of therapeutic strategies.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"5 ","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000326/pdfft?md5=2d212fc091322286f662f766c42e3532&pid=1-s2.0-S2667394022000326-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44690690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of inflammations and EMT in carcinogenesis","authors":"Md Shariful Islam , Md Reaz Morshed , Golap Babu , Md Asaduzzaman Khan","doi":"10.1016/j.adcanc.2022.100055","DOIUrl":"10.1016/j.adcanc.2022.100055","url":null,"abstract":"<div><p>Cancer is one of the major health burdens in modern world, and its mechanism is very complex, which is one of the main reasons for difficulties in cancer drug development. The development of cancer is associated with chronic inflammation, although inflammation is an essential biological process. The epithelial-mesenchymal transition (EMT) is a crucial step in development process of human tissue and involve in the regulatory pathways. On the contrary, the uncontrolled EMT is responsible for the initiation of cancer, its metastasis, immunosuppression, and resistance to antitumor treatment. Interestingly, there is an interrelationship between inflammation and EMT process. Usually, proinflammatory cytokines activate EMT inducing transcription factors (EMT-TFs), causing epithelial cells to change into cancerous mesenchymal cell by activating the mesenchymal cells markers, such as N- Cadherin, Fibronectin, Vimentin etc., and inhibiting the epithelial cells markers such as E− Cadherin, Claudin 1, Occludin, and β-catenin. Consequently, epithelial cells are dissociated, invasive, motile, resistant to therapy, resistant to apoptosis, and undergo mesenchymal cells angiogenesis. Some natural products and short RNAs have been identified to interfere with inflammation-EMT axis to inhibit cancer progression and metastasis. We have described these relationships in this review article and also described the therapeutic perspectives for cancer.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"5 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000296/pdfft?md5=b3b225e324ee3ca5be1e6c5ec9cec112&pid=1-s2.0-S2667394022000296-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42209959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sharmin Chowdhury , Sheikh Joly Ferdous Ara , Shirazum Monira Mili , Tahani Momotaz , Md Maruf Ahmed Molla , Shaheda Anwar , Ahmed Abu Saleh
{"title":"Mutational profile of KRAS, NRAS, BRAF, PIK3CA, and AKT1 genes in colorectal cancer patients in a tertiary care hospital, Dhaka","authors":"Sharmin Chowdhury , Sheikh Joly Ferdous Ara , Shirazum Monira Mili , Tahani Momotaz , Md Maruf Ahmed Molla , Shaheda Anwar , Ahmed Abu Saleh","doi":"10.1016/j.adcanc.2022.100054","DOIUrl":"10.1016/j.adcanc.2022.100054","url":null,"abstract":"<div><h3>Background</h3><p>Colorectal carcinoma (CRC) is the third most common cancer in the world and incidences are on the rise in Bangladesh. <em>KRAS, NRAS, BRAF, PIK3CA</em>, and <em>AKTI</em> gene mutations are predictive markers of biological therapies, monoclonal antibodies targeting EGFR. The purpose of this study was to detect <em>KRAS, NRAS, BRAF, PIK3CA</em>, and <em>AKT1</em> genes mutation in CRC patients by multiplex real-time Polymerase Chain Reaction (PCR) and evaluate the association of the mutations with clinicopathological features.</p></div><div><h3>Methodology</h3><p>This cross-sectional study was carried out in the Department of Microbiology & Immunology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2019 to January 2020. Tissues from surgically resected colorectal tumors were collected from 44 histopathologically confirmed adult colorectal cancer patients, who were admitted in the Department of Colorectal Surgery, BSMMU.</p></div><div><h3>Results</h3><p>Among 44 histopathologically diagnosed colorectal cancer patients, <em>KRAS, BRAF</em>, and <em>PIK3CA</em> gene mutations were identified in 31.5%, 4.85%, and 4.85% tumors, respectively. In this study, no mutation was detected in <em>NRAS</em> and <em>AKT1</em> genes. Concurrent mutation in <em>KRAS</em> and <em>PIK3CA</em> genes were found in one patient. Among the 14 <em>KRAS</em> mutant cases, most (92.85%) were in exon 2 (codon 12/13) and only 7.15% of the mutations were in exon 3 (codon 61). No mutation was detected in codon 59, 117, and 146. Among the two <em>PIK3CA</em> mutations, one was present in exon 9 and another was in exon 20. <em>KRAS</em> mutations were significantly associated with well and moderately differentiated tumors than poorly differentiated tumors (p < 0.05). Histopathologically there was no significant association of <em>KRAS</em> mutations with age, sex, tumor location, TNM staging, and other parameters.</p></div><div><h3>Conclusion</h3><p>A combined evaluation of genetic biomarkers can classify about one-third of colorectal cancer patients as mutant for any one of these <em>KRAS, BRAF</em>, and <em>PIK3CA</em> genes.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"5 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000284/pdfft?md5=b86cf9836a1cb43a421bff404a03877e&pid=1-s2.0-S2667394022000284-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48436874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tasneem Khan , Mohhammad A. Altamimi , Afzal Hussain , Mohhammad Ramzan , Sumel Ashique , Mohammed R. Alhuzani , Osamah Abdulrahman Alnemer , Tahir Khuroo , Hisham Abdulaziz Alshammari
{"title":"Understanding of PSA biology, factors affecting PSA detection, challenges, various biomarkers, methods, and future perspective of prostate cancer detection and diagnosis","authors":"Tasneem Khan , Mohhammad A. Altamimi , Afzal Hussain , Mohhammad Ramzan , Sumel Ashique , Mohammed R. Alhuzani , Osamah Abdulrahman Alnemer , Tahir Khuroo , Hisham Abdulaziz Alshammari","doi":"10.1016/j.adcanc.2022.100059","DOIUrl":"10.1016/j.adcanc.2022.100059","url":null,"abstract":"<div><p>Cancer is a global challenge for healthcare professional due to multiple unresolved issues before therapy, during therapy, and post-therapy stages. The disease diagnosis and subsequent chemotherapy are an ideal treatment approach to culminate such menace. Among cancers, prostate cancer (PC) is considered next to skin and breast cancer as the most dreadful and recorded with high mortality. It is also one of the leading causes of cancer death among men. With increased incidence worldwide and high mortality rate prostate cancer remains a global healthcare challenge. Advances in the diagnosis of PC have improved the chances of patient survival. Today, scientists developed electrochemical biosensors for early diagnosis of PC and it was found to be playing a significant role to reduce cases, mortality and complication at clinical set up. This updated review focused on biomarkers and traditional techniques used for PC diagnosis (early) and the most recent achievements of electrochemical techniques for making successful translation to clinical bed. Nanoparticles based electro-biochemical techniques have gained considerable attention alternative to traditional techniques. These techniques are found significantly effective for PC detection and have shown interesting parameters such as low cost and easy incorporation to user-friendly sensing platforms. With further advancements portable devices can be developed that can diagnose PC earlier for rapid clinical analysis and subsequently earliest report availability to the physician office for quick decision and life-saving approach. Overall, these compiled data in a form of review paper supports the adoption and promotion of nanotechnology-based diagnostics for PC in the healthcare.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"5 ","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000338/pdfft?md5=d4a0e524b426574a10bbfa3d5410c418&pid=1-s2.0-S2667394022000338-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43873595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The possibility of bowel metastasis in patient repeatedly irradiated due to recurrent cervical cancer","authors":"Na Rae Kim , Seok Ho Lee","doi":"10.1016/j.adcanc.2022.100060","DOIUrl":"10.1016/j.adcanc.2022.100060","url":null,"abstract":"<div><p>Cases of cervical cancer metastatic to the bowel are not rare because recurrent cervical cancer can commonly metastasize to nearby structures by direct extension. However, in recurrent cervical cancer patients who have received repeated radiation therapy, the treatment approach for acute abdominal pain has been generally established based on the first diagnostic impression of radiation enteritis. Therefore, we want to report with the aim of notifying that the possibility of bowel metastasis, especially in patients who have repeatedly received radiation therapy for recurrent cervical cancer, should also be considered not only for radiation enteritis. Here, we report the case which showed the clinical diagnosis of radiation enteritis after receiving repeated radiation therapy for recurrent cervical cancer, but showed the final pathologic diagnosis of bowel metastasis.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"5 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266739402200034X/pdfft?md5=e764572d20468280721ef894c0aa6674&pid=1-s2.0-S266739402200034X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48415632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Li, Yue Li, Hina Rehmani, Jianhui Guo, Ravi Padia, Ozlem Calbay, Zuo Ding, Yunhan Jiang, Lingtao Jin, Shuang Huang
{"title":"Attenuated miR-203b-3p is critical for ovarian cancer progression and aptamer/miR-203b-3p chimera can be explored as a therapeutic","authors":"Tao Li, Yue Li, Hina Rehmani, Jianhui Guo, Ravi Padia, Ozlem Calbay, Zuo Ding, Yunhan Jiang, Lingtao Jin, Shuang Huang","doi":"10.1016/j.adcanc.2022.100031","DOIUrl":"10.1016/j.adcanc.2022.100031","url":null,"abstract":"<div><p>MicroRNAs (miRNAs) are actively involved in the progression and metastasis of ovarian cancer. Here we show that miR-203b–3p is one of the miRNAs whose expression is diminished in advanced ovarian cancer (Stage III/IV). Introducing miR-203b-3p into ovarian cancer cells suppressed cell migration, <em>in vitro</em> invasion and peritoneal metastatic colonization. With the aid of cytokine array and modified Cross-Linking, Ligation, and Sequencing of Hybrids (qCLASH), we identified C-X-C motif chemokine ligand 1 (CXCL1) mRNA as a target of miR-203b-3p. Recombinant CXCL1 largely restored cell migration/invasion and CXCL1 neutralizing antibody blocked cell migration/invasion. Intriguingly, miR-203b-3p targets CXCL1 in an unconventional manner: 1) miR-203b-3p targets the 5′-untranslated region (UTR) and protein coding region of CXCL1 mRNA and 2) seed sequences in miR-203b-3p are not the conventional nucleotides 2 to 8 observed for most of miRNA/target complementation. Finally, we show that epithelial cell adhesion molecule (EpCAM) aptamer can effectively deliver miR-203b-3p into ovarian cancer cells and EpCAM aptamer-delivered miR-203b-3p impeded peritoneal metastatic colonization and prolonged lifespan of tumor-bearing mice. In summary, our findings provide a novel mechanism in which attenuated miR-203b-3p expression sustains CXCL1 abundance and hence ovarian cancer progression. Importantly, we suggest that EpCAM aptamer-delivered miR-203b-3p may be exploited for therapeutic purpose against advanced ovarian cancer.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000053/pdfft?md5=aea384b9da14022630466472dc094058&pid=1-s2.0-S2667394022000053-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48211540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}