PRP4 Promotes Skin Cancer by Inhibiting Production of Melanin, Blocking Influx of Extracellular Calcium, and Remodeling Cell Actin Cytoskeleton
Pre-mRNA processing factor 4B (PRP4) has previously been shown to induce epithelial-mesenchymal transition (EMT) and drug resistance in cancer cell lines. As melanin plays an important photoprotective role in the risk of sun-induced skin cancers, we have investigated whether PRP4 can induce drug res...
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description | Pre-mRNA processing factor 4B (PRP4) has previously been shown to induce epithelial-mesenchymal transition (EMT) and drug resistance in cancer cell lines. As melanin plays an important photoprotective role in the risk of sun-induced skin cancers, we have investigated whether PRP4 can induce drug resistance and regulate melanin biosynthesis in a murine melanoma (B16F10) cell line. Cells were incubated with a crucial melanogenesis stimulator, alpha-melanocyte-stimulating hormone, followed by transfection with PRP4. This resulted in the inhibition of the production of melanin via the downregulation of adenylyl cyclase-cyclic adenosine 3′,5′-monophosphate (AC)–(cAMP)–tyrosinase synthesis signaling pathway. Inhibition of melanin production by PRP4 leads to the promotion of carcinogenesis and induced drug resistance in B16F10 cells. Additionally, PRP4 overexpression upregulated the expression of β-arrestin 1 and desensitized the extracellular calcium-sensing receptor (CaSR), which in turn, inhibited the influx of extracellular Ca2+ ions. The decreased influx of Ca2+ was confirmed by a decreased expression level of calmodulin. We have demonstrated that transient receptor potential cation channel subfamily C member 1 was involved in the influx of CaSR-induced Ca2+ via a decreasing level of its expression. Furthermore, PRP4 overexpression downregulated the expression of AC, decreased the synthesis of cAMP, and modulated the actin cytoskeleton by inhibiting the expression of Ras homolog family member A (RhoA). Our investigation suggests that PRP4 inhibits the production of melanin in B16F10 cells, blocks the influx of Ca2+ through desensitization of CaSR, and modulates the actin cytoskeleton through downregulating the AC–cAMP pathway; taken together, these observations collectively lead to the promotion of skin carcinogenesis. |
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As melanin plays an important photoprotective role in the risk of sun-induced skin cancers, we have investigated whether PRP4 can induce drug resistance and regulate melanin biosynthesis in a murine melanoma (B16F10) cell line. Cells were incubated with a crucial melanogenesis stimulator, alpha-melanocyte-stimulating hormone, followed by transfection with PRP4. This resulted in the inhibition of the production of melanin via the downregulation of adenylyl cyclase-cyclic adenosine 3′,5′-monophosphate (AC)–(cAMP)–tyrosinase synthesis signaling pathway. Inhibition of melanin production by PRP4 leads to the promotion of carcinogenesis and induced drug resistance in B16F10 cells. Additionally, PRP4 overexpression upregulated the expression of β-arrestin 1 and desensitized the extracellular calcium-sensing receptor (CaSR), which in turn, inhibited the influx of extracellular Ca2+ ions. The decreased influx of Ca2+ was confirmed by a decreased expression level of calmodulin. We have demonstrated that transient receptor potential cation channel subfamily C member 1 was involved in the influx of CaSR-induced Ca2+ via a decreasing level of its expression. Furthermore, PRP4 overexpression downregulated the expression of AC, decreased the synthesis of cAMP, and modulated the actin cytoskeleton by inhibiting the expression of Ras homolog family member A (RhoA). Our investigation suggests that PRP4 inhibits the production of melanin in B16F10 cells, blocks the influx of Ca2+ through desensitization of CaSR, and modulates the actin cytoskeleton through downregulating the AC–cAMP pathway; taken together, these observations collectively lead to the promotion of skin carcinogenesis.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22136992</identifier><identifier>PMID: 34209674</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Actin ; Adenosine ; Adenylate cyclase ; Arrestin ; Biosynthesis ; Calcium (extracellular) ; Calcium influx ; Calcium ions ; Calcium-binding protein ; Calcium-sensing receptors ; Calmodulin ; Carcinogenesis ; Carcinogens ; Cell adhesion & migration ; Cell cycle ; Cell growth ; Cyclic AMP ; Cyclin-dependent kinases ; Cytoskeleton ; Desensitization ; Drug resistance ; Homology ; Investigations ; Kinases ; Melanin ; Melanocyte-stimulating hormone ; Melanoma ; Mesenchyme ; Morphology ; mRNA ; mRNA processing ; Mutation ; Post-transcription ; Proteins ; RhoA protein ; Signal transduction ; Skin cancer ; Stimulators ; Transcription factors ; Transfection ; Tumor cell lines ; Tyrosinase</subject><ispartof>International journal of molecular sciences, 2021-07, Vol.22 (13), p.6992</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-9ef5108bbec8263faf50d18cc7e5dbabcf6bde1d3ce8052afddeffd4d8dc4d283</citedby><cites>FETCH-LOGICAL-c389t-9ef5108bbec8263faf50d18cc7e5dbabcf6bde1d3ce8052afddeffd4d8dc4d283</cites><orcidid>0000-0002-5841-6506 ; 0000-0001-6692-0270</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268783/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268783/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Ahmed, Muhammad Bilal</creatorcontrib><creatorcontrib>Islam, Salman Ul</creatorcontrib><creatorcontrib>Lee, Young Sup</creatorcontrib><title>PRP4 Promotes Skin Cancer by Inhibiting Production of Melanin, Blocking Influx of Extracellular Calcium, and Remodeling Cell Actin Cytoskeleton</title><title>International journal of molecular sciences</title><description>Pre-mRNA processing factor 4B (PRP4) has previously been shown to induce epithelial-mesenchymal transition (EMT) and drug resistance in cancer cell lines. As melanin plays an important photoprotective role in the risk of sun-induced skin cancers, we have investigated whether PRP4 can induce drug resistance and regulate melanin biosynthesis in a murine melanoma (B16F10) cell line. Cells were incubated with a crucial melanogenesis stimulator, alpha-melanocyte-stimulating hormone, followed by transfection with PRP4. This resulted in the inhibition of the production of melanin via the downregulation of adenylyl cyclase-cyclic adenosine 3′,5′-monophosphate (AC)–(cAMP)–tyrosinase synthesis signaling pathway. Inhibition of melanin production by PRP4 leads to the promotion of carcinogenesis and induced drug resistance in B16F10 cells. Additionally, PRP4 overexpression upregulated the expression of β-arrestin 1 and desensitized the extracellular calcium-sensing receptor (CaSR), which in turn, inhibited the influx of extracellular Ca2+ ions. The decreased influx of Ca2+ was confirmed by a decreased expression level of calmodulin. We have demonstrated that transient receptor potential cation channel subfamily C member 1 was involved in the influx of CaSR-induced Ca2+ via a decreasing level of its expression. Furthermore, PRP4 overexpression downregulated the expression of AC, decreased the synthesis of cAMP, and modulated the actin cytoskeleton by inhibiting the expression of Ras homolog family member A (RhoA). Our investigation suggests that PRP4 inhibits the production of melanin in B16F10 cells, blocks the influx of Ca2+ through desensitization of CaSR, and modulates the actin cytoskeleton through downregulating the AC–cAMP pathway; taken together, these observations collectively lead to the promotion of skin carcinogenesis.</description><subject>Actin</subject><subject>Adenosine</subject><subject>Adenylate cyclase</subject><subject>Arrestin</subject><subject>Biosynthesis</subject><subject>Calcium (extracellular)</subject><subject>Calcium influx</subject><subject>Calcium ions</subject><subject>Calcium-binding protein</subject><subject>Calcium-sensing receptors</subject><subject>Calmodulin</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cyclic AMP</subject><subject>Cyclin-dependent kinases</subject><subject>Cytoskeleton</subject><subject>Desensitization</subject><subject>Drug resistance</subject><subject>Homology</subject><subject>Investigations</subject><subject>Kinases</subject><subject>Melanin</subject><subject>Melanocyte-stimulating hormone</subject><subject>Melanoma</subject><subject>Mesenchyme</subject><subject>Morphology</subject><subject>mRNA</subject><subject>mRNA processing</subject><subject>Mutation</subject><subject>Post-transcription</subject><subject>Proteins</subject><subject>RhoA protein</subject><subject>Signal transduction</subject><subject>Skin cancer</subject><subject>Stimulators</subject><subject>Transcription factors</subject><subject>Transfection</subject><subject>Tumor cell lines</subject><subject>Tyrosinase</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc9uEzEQxlcIREvhxgNY4sIhAf_bjX1BKlEpkYqICpwtrz1unXjt1t5FzVP0lfGqFSqcZqTvp2--mWmatwR_YEzij343FEoJ66Skz5pjwildYtytnj_pj5pXpewwpoy28mVzxDjFslvx4-Z-e7nlaJvTkEYo6MfeR7TW0UBG_QFt4rXv_ejj1YzYyYw-RZQc-gZBRx8X6HNIZj_rm-jCdDdrZ3dj1gZCmILO1SwYPw0LpKNFlzAkC2Hm1xVAp9WwzjuMqewhwJji6-aF06HAm8d60vz6cvZz_XV58f18sz69WBom5LiU4FqCRd-DEbRjTrsWWyKMWUFre90b1_UWiGUGBG6pdtaCc5ZbYQ23VLCT5tOD783UD2ANxBo6qJvsB50PKmmv_lWiv1ZX6beq48RKsGrw_tEgp9sJyqgGX-atdYQ0FUVbLni9Pe4q-u4_dJemHOt6MyU5IVLOiRYPlMmplAzubxiC1fxp9fTT7A9qPZ7V</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Ahmed, Muhammad Bilal</creator><creator>Islam, Salman Ul</creator><creator>Lee, Young Sup</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5841-6506</orcidid><orcidid>https://orcid.org/0000-0001-6692-0270</orcidid></search><sort><creationdate>20210701</creationdate><title>PRP4 Promotes Skin Cancer by Inhibiting Production of Melanin, Blocking Influx of Extracellular Calcium, and Remodeling Cell Actin Cytoskeleton</title><author>Ahmed, Muhammad Bilal ; 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As melanin plays an important photoprotective role in the risk of sun-induced skin cancers, we have investigated whether PRP4 can induce drug resistance and regulate melanin biosynthesis in a murine melanoma (B16F10) cell line. Cells were incubated with a crucial melanogenesis stimulator, alpha-melanocyte-stimulating hormone, followed by transfection with PRP4. This resulted in the inhibition of the production of melanin via the downregulation of adenylyl cyclase-cyclic adenosine 3′,5′-monophosphate (AC)–(cAMP)–tyrosinase synthesis signaling pathway. Inhibition of melanin production by PRP4 leads to the promotion of carcinogenesis and induced drug resistance in B16F10 cells. Additionally, PRP4 overexpression upregulated the expression of β-arrestin 1 and desensitized the extracellular calcium-sensing receptor (CaSR), which in turn, inhibited the influx of extracellular Ca2+ ions. The decreased influx of Ca2+ was confirmed by a decreased expression level of calmodulin. We have demonstrated that transient receptor potential cation channel subfamily C member 1 was involved in the influx of CaSR-induced Ca2+ via a decreasing level of its expression. Furthermore, PRP4 overexpression downregulated the expression of AC, decreased the synthesis of cAMP, and modulated the actin cytoskeleton by inhibiting the expression of Ras homolog family member A (RhoA). Our investigation suggests that PRP4 inhibits the production of melanin in B16F10 cells, blocks the influx of Ca2+ through desensitization of CaSR, and modulates the actin cytoskeleton through downregulating the AC–cAMP pathway; taken together, these observations collectively lead to the promotion of skin carcinogenesis.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>34209674</pmid><doi>10.3390/ijms22136992</doi><orcidid>https://orcid.org/0000-0002-5841-6506</orcidid><orcidid>https://orcid.org/0000-0001-6692-0270</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Actin Adenosine Adenylate cyclase Arrestin Biosynthesis Calcium (extracellular) Calcium influx Calcium ions Calcium-binding protein Calcium-sensing receptors Calmodulin Carcinogenesis Carcinogens Cell adhesion & migration Cell cycle Cell growth Cyclic AMP Cyclin-dependent kinases Cytoskeleton Desensitization Drug resistance Homology Investigations Kinases Melanin Melanocyte-stimulating hormone Melanoma Mesenchyme Morphology mRNA mRNA processing Mutation Post-transcription Proteins RhoA protein Signal transduction Skin cancer Stimulators Transcription factors Transfection Tumor cell lines Tyrosinase |
title | PRP4 Promotes Skin Cancer by Inhibiting Production of Melanin, Blocking Influx of Extracellular Calcium, and Remodeling Cell Actin Cytoskeleton |
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